What determines testosterone exposure in womb, baby's genetics or mom's body?

What determines testosterone exposure in womb, baby's genetics or mom's body?

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I read this article which has the following quote:

The ratio between index and ring finger is believed to be linked to exposure to the male hormone testosterone in the womb.

And I wonder what determines the amount of exposure to testosterone in the womb. Is it testosterone produced by the fetus itself, in which case the baby's own genetics is the answer, or does this exposure the article speaks of more likely refer to testosterone produced by the mother and exposed to the baby?

Fetal testis produces testosterone from cholesterol. There is a peak of production around 15 weeks of gestation (the "masculinization programming window"). So the genotype of the fetus can affect testosterone levels directly via effects on the biosynthesis of the hormone, or indirectly by defective regulation of the pathway's activity.

However, exposure to chemicals in the mother's environment is also thought to play a part in determining testosterone levels. The classic example of this is the phthalate esters used as plasticizers.

Scott et al. (2009) Steroidogenesis in the Fetal Testis and Its Susceptibility to Disruption by Exogenous Compounds. Endocrine Reviews 30: preprint freely available here.

It has long been evident that human fetuses produce the hormones that dominate their development in utero. (Ref: Robinson et. al., J Clin Endocrinol Metab. 1977 Oct;45(4):755-61. Amniotic fluid androgens and estrogens in midgestation.)

There is a baseline increase in maternal testosterone during pregnancy regardless of fetal sex, and I can't find whether that is due to production by the mother's endocrine systems vs. transfer from the fetus. But in any case transfer from the fetus dominates: A male fetus produces so much testosterone that the serum levels detectable in the mother's blood ranges up to 4 times the amount found in typical non-pregnant women! (Ref: Meulenberg & Hofman, J Steroid Biochem Mol Biol. 1991 Jul;39(1):51-4. Maternal testosterone and fetal sex.)

Talk:Prenatal hormones and sexual orientation

It seems that the content was moved from homosexuality and has ended up here, in a somewhat incoherent form. As I often do, I started editing this page to fix sloppy writing, find references etc, and ended up seeing deeper problems. It's an interesting topic and deserves to be treated properly.

Firstly, is 'fetal hormones and sexual orientation' the best title for this article? The fetal stage covers the period from the end of the 8th week to birth. But sex differentiation is already occurring at the zygote and embyonic stage. So perhaps 'Prenatal hormones and sexual orientation' is better? (I'm no biologist).

I'd be happy with "prenatal" as a broader description. I think the existing hypotheses really are fetal (or at least that's how they get reported), but that's a good generalization. We should have a redirect if we rename though. Lulu of the Lotus-Eaters 07:07, 2005 August 31 (UTC)

Secondly, the article has a lot of content not directly related to hormones — it's making a more general argument about a biological basis for sexual orientation. It explores links between gender and sexual orientation, and refers to studies that imply a genetic rather than hormonal cause. So I propose either this content is moved elsewhere (more than half of the article) or the broader scope of the article is indicated in its title and introduction (eg Biological basis for sexual orientation). Any thoughts?

Hmmm. that's probably better. It could have subcategories. But there's already a rather mediocre page at Biology_and_sexual_orientation, and it contains some overlapping material with this. I think the best approach might be to snip the good parts from Biology_and_sexual_orientation, and move them into Prenatal hormones and sexual orientation (either cutting with a "see also" back to here, or copying with some duplication). Lulu of the Lotus-Eaters 07:07, 2005 August 31 (UTC)

Thirdly, does anyone have a reference for the Reiner study? I found a similar study of his on the web but the conclusions are quite different to what is presented here. — ntennis 06:07, 31 August 2005 (UTC)

I dunno, there's an anon editor who was pushing this fetal hormone stuff on the Talk:Homosexuality page, and my first draft was just a copy of what he proposed (maybe slight cleanup). You could see if that IP address can be reached: User: I was hoping that after I created the page s/he would hop in here to improve it. Lulu of the Lotus-Eaters 07:07, 2005 August 31 (UTC)

There is already a page for the broader argument: Biology and sexual orientation. I propose that all non-hormone related stuff here is merged there. ntennis 06:19, 31 August 2005 (UTC)

Here is the Reiner study from the Boston Globe article:

Males and females have a fundamental genetic difference - females have two X chromosomes, and males have an X and a Y. Still, right after conception, it's hard to tell male and female zygotes apart, except for that tucked-away chromosomal difference. Normally, the changes take shape at a key point of fetal development, when the male brain is masculinized by sex hormones. The female brain is the default. The brain will stay on the female path as long as it is protected from exposure to hormones. The hormonal theory of homosexuality holds that, just as exposure to circulating sex hormones determines whether a fetus will be male or female, such exposure must also influence sexual orientation. The cases of children born with disorders of "sexual differentiation" offer insight. William Reiner, a psychiatrist and urologist with the University of Oklahoma, has evaluated more than a hundred of these cases. For decades, the standard medical response to boys born with severely inadequate penises (or none at all) was to castrate the boy and have his parents raise him as a girl. But Reiner has found that nurture - even when it involves surgery soon after birth - cannot trump nature. Of the boys with inadequate penises who were raised as girls, he says, "I haven't found one who is sexually attracted to males." The majority of them have transitioned back to being males and report being attracted to females. During fetal development, sexual identity is set before the sexual organs are formed, Reiner says. Perhaps it's the same for sexual orientation. In his research, of all the babies with X and Y chromosomes who were raised as girls, the only ones he has found who report having female identities and being attracted to males are those who did not have "receptors" to let the male sex hormones do their masculinizing in the womb. What does this all mean? "Exposure to male hormones in utero dramatically raises the chances of being sexually attracted to females," Reiner says. "We can infer that the absence of male hormone exposure may have something to do with attraction to males." 05:33, 7 September 2005 (UTC)

Good for Reiner. of course, the rest of us know that we can NOT infer this we can only hypothesize this, and then try to design and implement experiments to test the hypothesis.

Note: Just putting this here for safe keeping. The tone is way too informal for the article itself, but I'd like to work something in about degrees of correlation suggested. Lulu of the Lotus-Eaters

Actually, my citation can be the very same 2000 Breedlove study that our friend in Farmington includes in Fetal hormones and sexual orientation. Background is that length of ring finger relative to index finger is strongly correlated with fetal testosterone levels. That fact is rather well established quite apart from sexual orientation. Breedlove found an additional much weaker correlation between implied fetal testosterone and sexual orientation, with lesbians in particularly being most strongly androgynized. It's definitely interesting. Gay men show the same pattern (gays more androgynized), but to a smaller degree.

No gay men were shown to be more ANDROGENized androgens are male hormones such as testosterone

However, there is a huge overlap between the suggested fetal testosterone levels and sexual orientation. That is, on average of a bunch of lesbians had higher fetal testosterone than a paired group of straight women. But many lesbians had lower fetal testosterone than the straight-woman average. And many straight women had higher fetal testosterone than the lesbian average. The standard deviation within each group is much more than the mean difference between the groups.

So what does it show? Well, I dunno. There's something potentially interesting there, especially if it can be replicated in much larger samples. But it's hardly clear causation, nor even clear correlation. What it amounts to might be something like (purely hypothetically): "High testesterone exposure female fetuses have a 10% chance of becoming lesbian low testosterone exposure female fetuses have a 5% chance of becoming lesbian." But that's about the strongest conclusion I can imagine coming out of this (and it hasn't yet, it's been suggested), and that's a relatively weak factor. Lulu of the Lotus-Eaters 23:00, 2005 August 21 (UTC)

There are a quite a few studies looking at digit ratio and sexual orientation. Five of the best are compared by Dennis Mcfadden (in McFadden et el. 2005. A Reanalysis of Five Studies on Sexual Orientation and the Relative Length of the 2nd and 4th Fingers (the 2D:4D Ratio). Archives of Sexual Behavior 34, 341--356.). Another study finds a difference in digit ratio between identical twins that are discordant for sexual orientation (Hall & Love, 2003. Finger-length ratios in female monozygotic twins discordant for sexual orientation. Archives Sexual Behavior 32, 23-28. Pete.Hurd 06:15, 10 September 2005 (UTC) Hmmm. there must be a pretty darn small sample size of female monozygotes who are discordant on sexual orientation (and who can be located, and are willing to participate in a study). Oddly, I happen to know such a pair and they happen to be the daughters of a famous researcher on genetic/behavioral causation (of schizophrenia, not of sexual orientation). Since I don't have easy access to McFadden's survey, can you say what it says? Are effects consistent in direction, as surveyed? What is the relative size of the effect versus the size of the statndard deviations within each sexual orientation, in the aggregate? Etc. Lulu of the Lotus-Eaters 04:17, 19 September 2005 (UTC)

The article mentions a 1993 study demonstrating a fraternal birth order effect. This should be provided (and added to the fraternal birth order page). Pete.Hurd 03:58, 19 September 2005 (UTC)

As I understand it, the fraternal birth order effect is not thought to be directly hormonal. I can understand that the topic is so closely related to prenatal hormones and sexual orientation that it might belong here, but it makes me wonder why this page isn't part of Biology_and_sexual_orientation. This page really needs a lot of work (but so does the material covering this topic on Biology_and_sexual_orientation page. Pete.Hurd 04:12, 19 September 2005 (UTC)

My feeling is still that this topic is distinct enough that a separate article is warranted, but with appropriately prominent links in both directions to/from Biology and sexual orientation. Then again, I'm a big fan of relatively small self-contained articles over really long, multi-sectioned and exhaustive treatments of all related facets. Lulu of the Lotus-Eaters 04:35, 19 September 2005 (UTC) Makes sense, the long articles are hard to read. In a perfect workd I think this one would be called uterine effects on sexual orientation, but the present one might make more sense. Pete.Hurd 05:06, 19 September 2005 (UTC)

It is critical to note that these studies still require that homosexuals show a significant heritable component and that this evidence is scarce and difficult to obtain.

Specifically, the production prental hormones is genetically controlled.

Despite this, there is certainly not a preponderance of reliable, statistically significant, and reproducible scientific evidence to support this theory. At best, there is only enough evidence to suggest that further work is necessary.

There is no reason why the hypothesis of prenatal hormones affecting/determining sexual orientation would require any heritable component of sexual orientation. The former hypothesis does not rule out the latter, but they are quite independent. Yes, I can see that a genetic effect on uterine hormone production could be heritable but it being so is not a logical necessity, just another potentially testable hypothesis. Lulu of the Lotus-Eaters 14:52, 29 October 2005 (UTC)

About a year or two before the Berlin Wall came down (1987-1988), I recall seeing a brief report on the television network news about work done by an East German doctor, using rats. He had been intrigued by the spike in homosexuality among boys born in Germany during World War II, and to test his theory, subjected pregnant rats to stresses, such as keeping them in claustrophobic conditions and forcing them to swim until exhaustion. His studies supported the idea of hormonal imbalances caused by stress in mothers contributing to homosexual tendencies in their offspring. A recent Google search turned up nothing. Does any Wikipedian have a clue where to find information on these studies? I think it would be worthwhile to include it in this article. --Quicksilver T @ 00:19, 1 December 2005 (UTC)

  • Ward, I. (1972) Prenatal stress feminizes and demasculinizes the behavior of males. "Science" 175:82-84
  • Ward et al (2002) Hormonal Mechanisms Underlying Aberrant Sexual Differentiation in Male Rats Prenatally Exposed to Alcohol, Stress, or Both. Archives of Sexual Behavior 31:9-16
  • Ward et al (2003) Fetal testosterone surge: specific modulations induced in male rats by maternal stress and/or alcohol consumption. Hormones and Behavior 43:531-539

I also have a vague tingly feeling that Milton Diamond did some rodent work, (1960's?), but I can't find those references just now. I'm assuming you are aware of Lee Ellis' work, as in

  • Ellis, L. et al (1988) Sexual orientation of human offspring may be altered by severe maternal stress during pregnancy. Journal of Sex Research 25:152--157.
  • Ellis, L. & Cole-Harding, S. (2001) The effects of prenatal stress, and of prenatal alcohol and nicotine exposure, on human sexual orientation. Physiol. Behav. 74:213--226

The thing with rodents, is that while various things may influence sexual behaviour, it is kind of hard to equate it with sexual orientation without waving the hands a bit. Cheers, Pete.Hurd 07:12, 1 December 2005 (UTC)

Is Ewald's hypothesis that a virus causes homosexuality in all the species (or even, say, just all the mammals) which exhibit homosexuality, or only in humans? Lulu of the Lotus-Eaters 18:33, 23 December 2005 (UTC)

I've never heard of this theory. Is there any evidence to support it? Doubtful. In fact, some evolutionary biologists explain the persistence of homosexuality as an evolutionary advantage. For example, if a gay uncle doesn't have any of his own kids, his resources will go towards raising his nieces and nephews, in effect perpetuating his own genes through familial altruism. Do we have a reference for any progress in the mentioned "research"? If not, I suggest eliminating this section. Any thoughts?Gimmethoseshoes (talk) 21:08, 15 March 2008 (UTC)

I'm rewriting the section pertaining to prenatal hormones in summary style. The following info was in the section before I hacked away at it, so it could be useful here:

  • Observed differences in three areas of the brain in homosexual vs. heterosexual men (the anterior commisure, the supra-chiasmatic nucleus and the interstitial nuclei of the anterior hypothalamus, showing sexual diphormism, although their relation with homosexuality is not clear yet).[1]
  • Observed differences in cognitive testing showing results for homosexual men typical of heterosexual women and results for homosexual women typical of heterosexual men.
  • Observed differences in the preferences that homosexual men, heterosexual men, and heterosexual women have for the age of their sexual partners.

I've read that some researchers had made ties between prenatal hormones and contraception, suggesting that things like the birth control pill could have an impact on male sexual orientation. ADM (talk) 02:09, 16 June 2009 (UTC)

Really don't think this article qualifies for B-class quality rating. Sxologist (talk) 23:21, 24 August 2020 (UTC)

Hello, not sure about this edit which replaced transsexualism with transgenderism. I'm assuming they should match the sources, so I'm not sure which would take precedence since transgenderism involves a broad definition of gender identity, whereas transsexualism implies the subset who change sex? Sxologist (talk) 11:11, 7 October 2020 (UTC)

Reverted that IP for reasons I stated in that edit summary. Simply revert something like that in the future. Don't know what the IP was going on about. Flyer22 Frozen (talk) 23:23, 7 October 2020 (UTC) Yup. It's a case of someone changing wording for WP:RGW reasons rather than following WP:V and WP:NOR. Crossroads -talk- 23:34, 7 October 2020 (UTC)

What determines testosterone exposure in womb, baby's genetics or mom's body? - Biology

Visit the SALMON Bookshop for recommended books on this topic

  • Overview and learning objectives
  • What do we mean by the terms sex and gender?
  • The development of gender identity: Nature or Nurture?
  • Development of male and female external genitalia
  • Activational and organizational effects of hormones
  • Feminization of male rat by castration in infancy
  • Masculinization of female pups by injection of testosterone in infancy
  • Summary of the effects of castration and testosterone treatment
  • Behaviours influenced by hormone exposure in infancy
  • Effect of testosterone on the brain
  • Are there sex differences in human behaviour?
  • Do hormones affect psychosexual differentiation in humans?
  • Studies of congenital adrenal hyperplasia:
    • activity and aggression
    • marriage and motherhood
    • gender role preference behaviours
    • sexual orientation

    The contents of this lecture should surprise and interest you. The heart of the lecture is a diagram showing two opposing views on the development of gender.
    Gender consists of three elements:

    • gender role: adoption of masculine or feminine behavioral traits that are deemed appropriate or characteristic of a particular sex
    • gender identity: a person's private, subjective sense of their own sex
    • sexual orientation / preference: erotic desire for people of same or different sex

    The widely held view that gender is the result of the nurture we receive as children is contrasted with the idea that gender is influenced with biological factors in our nature. The lecture explores some evidence that supports the latter position.

    A series of experiments showing that it is possible to effect the sexual behaviour of animals by manipulating hormones circulating in their bodies during early development is presented.

    An important message from these studies is that the mammalian brain and external genitalia tend to develop as female unless they are exposed to androgens in infancy.

    This finding has important implications for human development which are explored by presenting a study that suggests that girls that are exposed to testosterone in utero exhibit masculine behaviour patterns in adulthood.

    After studying the material on this page you should be able to:

    • define the terms sex and gender
    • describe the nature and nurture theories of gender development
    • describe the role of dihydrotestosterone in genital development
    • outline the stages in development of male and female external genitalia
    • distinguish between the organizational and activational effects of hormones
    • describe the effects of castration in infancy on the sexual behaviour of the male rat
    • describe the effects of androgen injection in infancy on the development of female sexual behaviour in the rat
    • list eight rat behaviours affected by hormone exposure in infancy
    • locate the sexually dimorphic nucleus in a sagittal section of rat brain
    • describe the effect of testosterone on the SDN
    • describe how to measure gender role behaviours
    • describe the changes in cortisol, ACTH, and androgen secretion in congenital adrenal hyperplasia
    • describe the psychological consequences of CAH
    • explain the term 'psychosexual neutrality at birth' and understand the implications of this term for raising children born with ambiguous external genitalia

    Gender is a psychological term which refers to our awareness and reaction to biological sex

    • gender is determined by biological, psychological and sociological factors
    • masculine and feminine are psychological terms which refer to a person's gender
    • Chromosomes
    • Gonads
    • Prenatal hormones
    • Internal accessory organs
    • External genital appearance
    • Pubertal hormones
    • Assigned gender
    • Gender identity
    • gender role: adoption of masculine or feminine behavioral traits that are deemed appropriate or characteristic of a particular sex
    • gender identity: a person's private, subjective sense of their own sex
    • sexual orientation / preference: erotic desire for people of same or different sex

    The development of gender identity: Nature or Nurture?

    Each of us has a gender identity - a private feeling that we are male or female. There are two fundamentally different explanations for how this develops.

    The most influential theory is that our gender is the result of environmental influences, particularly the way we are treated by our parents, guardians, friends and relatives. According to Dr John Money we are psychosexually neutral at birth, and our gender is a consequence of the nurture we receive as children.

    The less popular view is that gender may is the result of nature, particularly the effects of hormones on the developing brain.

    This is not a dry academic argument. The lives of a significant number of people have been changed as a result of the application of these theories.

    • How do you think theories of gender development might have influenced the way parents raise their children?

    This web page describes some of the evidence that suggests that gender may the result of exposure to hormones in the first few weeks of life.

    Development of male and female external genitalia

    Perhaps the first question asked by parents and relatives after a child is born is "What sex is the child?". According to the nurture view of psychosexual differentiation this is the point at which shaping the child's gender identity begins. But the process may have started many weeks before when the baby was developing in the mother's womb. This series of diagrams shows how the development of a child's external genitalia is affected by exposure to the androgen dihydrotestosterone.

    An important message from this diagram is that - regardless of genetic sex -

    • a child will develop female external genitalia unless it is exposed to dihydrotestosterone
    • a child will develop male external genitalia if it is exposed to dihydrotestosterone

    These diagrams are based on the drawings found in most textbooks that cover the the biological bases of sexual behaviour.

    Here is an animated diagram of the effects of androgen exposure on external genital development that will open in a new browser window.

    The 'Guevedoces' of the Dominican Republic. "During the early 1970s, Dr. Julianne Imperato, a Cornell endocrinologist, conducted an expedition to the Dominican Republic to investigate reports of an isolated village where children appearing to be girls turned into men at puberty. In the village, these children were known as 'guevedoces' (literally, penis at 12 years)." Their underlying pathology was found to be a deficiency of the enzyme 5-alpha Reductase which converts testosterone into 5 dihydrotestosterone

    The nature and nurture views of psychosexual development differ in the significance they attach to the importance of hormones in the development of behavioural differences between males and females.

    Hormones have two fundamentally different effects on sexual behaviour:
    Organizational effects refer to the effects of hormones during the early development of an animal
    Activational effects refer to the effects of hormones in the adult organism

    There is evidence that exposure to hormones during a critical period of development changes the way in which the organism reacts to hormones in adulthood. Notice that this does not mean that early exposure to hormones has a permanent effect on behaviour. Instead it suggests that exposure to hormones in infancy affects how the adult reacts to hormones.

    In other words, early exposure to hormones organizes the way behaviour is activated by hormones in adulthood. We need to spend a few moments reviewing how the activational effects of hormones on behaviour are measured.

    Hormones such as testosterone, estrogen and progesterone, activate sexual behaviour of adult male and female rats

    Many studies measure female sexual behaviour in terms of 'lordosis'. Lordosis refers to a characteristic posture in which the female rodent arches her back and moves her tail to permit penetration by the male.

    Sexual behaviour in male rats consists of three behaviours:

    • Mount: the animal assumes the copulatory position on top of the female and grasps her flanks, but does not not insert his penis into the female's vagina
    • Intromission: the male mounts the female and briefly (200-300 milliseconds) inserts his penis. . Semen is not released during intromissions or mounts.
    • After 10 to 12 intromissions spaced 20-30 seconds apart, the rat ejaculates semen.

    The activational effects of hormones are discussed in greater detail on a separate page of this website.

    This page focusses on the organizational effects of hormones.

    According to the nature theory of psychosexual differentiation, hormones organize the brain during development. In a nutshell:

    Treatment of female rats with testosterone in infancy causes them to become:

    The organizational effects of the presence or absence of testosterone are only apparent in adulthood when the organism is under the activational effects of testosterone or estrogen and progesterone.

    Feminization of male rat by castration in infancy

    Exposure to testosterone between about day 17 of gestation to day 8-10 of postnatal life organizes the brain of a male rat to determine how it will react to hormones in adulthood.

    If a male rat is castrated at birth, and then given an injection of estrogen in adulthood, it exhibits lordosis, - a female sexual response - when tested with a sexually vigorous male rat.

    If a male rat is castrated at birth, and then exposed to a female rat which is in estrus (heat) he will not mate with her.

    In contrast, if a normal male is injected with estrogen in adulthood it does not display the lordosis response in the presence of a sexually vigorous male rat. A normal male rat will mate with a female rat in estrus.

    Testosterone is thought to establish male circuits (masculinization), and inhibit the development of female brain circuits (defeminization).

    Masculinization of female pups by injection of testosterone in infancy

    The absence of testosterone organizes the brain of a female rat to determine how it will react to hormones in adulthood.

    If a female rat is injected with testosterone during infancy, and then given an injection of testosterone in adulthood, she will show male sexual responses - mount, intromission and ejaculation behaviours - when tested with a female rat in estrus.

    If a female rat is injected with testosterone during infancy, and then injected with estrogen in adulthood, she will not exhibit lordosis behaviour when she is tested with a sexually vigorous male rat.

    In contrast, if a normal female rat is injected with testosterone in adulthood, she will not exhibit male sexual behaviours.

    A normal female rat in estrus will exhibit lordosis when paired with a sexually vigorous male rat.

    Testosterone is thought to establish male circuits (masculinization), and inhibit the development of female brain circuits (defeminization).

    In the absence of testosterone brain circuits are feminized and demasculinized.

    Summary of the effects of male castration and female testosterone treatment

    Adult sexual behavior in the rat depends on whether the brain was organized by gonadal hormones during the first few days after birth.

    Normal adult males display mounting behavior because their brains were subjected to a dose of testosterone from the gonads just after birth. The same effect can be produced in females by injecting the hormone testosterone.

    Depriving male pups of testosterone by castrating them at birth results in a female brain organization. As adults these feminized males, like normal females, display very few attempts to mount, but a high frequency of lordosis when mounted.

    Behaviours influenced by hormone exposure in infancy
    Testosterone exposure in infancy affects a range of behaviours not just reproductive behaviours.

    A number of behaviours in rats are effected by testosterone exposure around birth. These include:

    • Intromission and ejaculation behaviours
    • Exploratory behaviour
    • Aggression
    • Play
    • Taste preference
    • Feeding
    • Active avoidance learning
    • Maze learning

    Exploratory behaviour is more extensive among female rats than among male rats. This behaviour is modified when female rats are injected with testosterone shortly after birth. The bar chart shows the frequency of defecation, which is inversely proportional to exploration, during a three minute open-field test. When the females had not been injected with testosterone after birth (left and centre groups) their boli count was significantly less than males. Females that had been masculinized defecated at the same rate as males.

    Effect of testosterone on the brain

    We have seen that early exposure to testosterone affects the external genitalia and adult behaviour, but does it also change the brain? This is an important question. There is evidence that the brains of male and female rodents are structurally different, and that this sexual dimorphism is caused by exposure to androgen during a critical period of development.

    An area of the hypothalamus at the base of the brain called the sexually dimorphic nucleus of the preoptic area (SDN-POA) is much larger in male rats than in females. These diagrams show the location of this sexual dimorphism. You can load an animation that explains the relationship between the saggital and coronal views of the brain in a separate browser window.

    • SDN : sexually dimorphic nucleus
    • POA : preoptic area
    • SDN-POA : sexually dimorphic nucleus of the preoptic area

    These pictures of sections through the preoptic area of the rat brain show that:

    • the SDN-POA is larger in male than female rats
    • the SDN-POA is larger in females that have been injected with testosterone (androgenized females) than normal females.

    The size of the sexually dimorphic nucleus is affected by the presence or absence of testosterone during a critical period around birth (neonatal) .

    • The SDN is larger in males than females
    • Females androgenized with a testosterone proprionate (TP) injection on day 4 have significantly larger SDN volume than control (oil-treated ) females
    • SDN volume is reduced in males castrated on day 1 compared with normal males (Gorski, 1980)

    Are there sex differences in human behaviour?

    Berenbaum (1999) has shown clear differences in activities and job interests between adolescent boys and girls. But gender role behaviours may be influenced by the media.

    She found that overall boys were more aggressive than girls most aggressive acts tended to involve boys fighting with other boys. The amount of aggression by boys directed towards girls and vice versa tended to be relatively low.

    Corrine argued that this sex difference in aggression was due to masculinization of the brain by testosterone

    We have already described how androgen masculinizes the external genitalia of a developing baby.

    Sometimes female embryos are exposed to abnormally high levels of androgen before birth. A small number of genetic females are born with ambiguous external genitalia. The most common cause of female pseudohermaphroditism is congenital adrenal hyperplasia (CAH) which occurs in about 1 in 5,000 to 15,000 live births. Congenital adrenal hyperplasia (CAH) also known as the adrenogenital syndrome (AGS).

    CAH is a disease that affects the manufacture of the "stress" hormone, cortisol. Cortisol is released into the blood stream from the adrenal gland, a small organ near the kidney.

    The diagram shows how a deficit in cortisol release disrupts the normal negative feedback between cortisol and ACTH secretion from the pituitary gland.

    In CAH patients a metabolic error causes overproduction of androgens (e.g. testosterone) in the adrenal gland. This androgen leads to partial masculinization of the external genitalia of female patients which is corrected surgically at birth and with artificial cortisol supplements.

    A great deal of attention has been given to the consequences of excess androgens on the psychosexual differentiation of these children.

    We will examine some early psychological studies of these girls (Ehrhardt, 1975) which suggests that exposure to androgen during development causes a partial masculinization of human female behaviour.

    Ehrhardt's study of fetally androgenized genetic female children
    This picture shows a baby girl born with congenital adrenal hyperplasia (CAH) . Her external genitalia have been partially masculinized (virilized) as a result of exposure to high levels of testesoterone whilst in the womb.

    Ehrhardt (1975) studied 17 female CAH patients: age 4.3 to 19.9 years, most of the girls were in middle childhood and early adolescence. The comparison sample (n=11) consisted of the girls' sisters who did not have CAH. All the patients were under long-term corrective treatment with replacement cortisol and had undergone surgical correction of the external genitalia, usually in infancy or early childhood. Interviews with children and their mothers, fathers and siblings were tape-recorded. Interview transcripts were rated according to coded scales to elicit information about the child's behaviour.
    Activity and aggression in congenital adrenal hyperplasia patients
    Girls with CAH were more often described as having high levels of energy expenditure compared to their unaffected siblings. They also tended to prefer to play with boys rather than other girls. Although they tended to start fights more frequently than their sisters, this difference was not statistically significant.

    Marriage and motherhood in congenital adrenal hyperplasia patients
    This diagram shows that girls with CAH were not very interested in playing with dolls, instead they tended to play with cars, trucks and blocks toys that are generally preferred by boys.

    They showed little interest in future roles as brides or mothers, but were much more concerned with their careers.

    Their relatives described them as being indifferent to - or avoiding - contact with babies. For example, they did not participate in caring for infants at home or go out babysitting.

    Gender role preference behaviours in congenital adrenal hyperplasia patients
    Relatives and girls with CAH describe themselves as 'tomboys' during all of their childhood.

    35% of the sample were unsure or said that they might have chosen to be a boy if they could start their lives over again. However, Ehrhardt points out that none of the girls were unsure about their gender identity. They did not feel that they were boys and being a girl did not make them unhappy. In other words - as a group - they did not exhibit gender dysphoria.

    Conclusion: CAH appears to have a significant effect on gender role behaviours. Patients exhibit significantly more male-typical behaviours than unaffected siblings.

    Sexual orientation in CAH/AGS patients
    Prenatal exposure to androgen could influence the development of:

    • sexual orientation - sex of preferred romantic partner and
    • gender identity - the feeling an individual has of being a man or a woman

    Money, Schwartz & Lewis (1984) asked 30 women born with CAH about their sexual orientation. Their replies are shown in this diagram together with an estimate of the base rate of female homosexuality according to Kinsey 1953. See Carlson for further details.

    Zucker et al (1996) review eight studies that have explored sexual orientation in women with CAH.

    Zucker et al (1996) found that most women with CAH have a female gender identity. However, significantly more women with CAH live as men than would be expected by chance.

    They conclude that "excessive exposure to prenatal androgens in women with CAH shifts psychosexual differentiation to a point somewhere in between a female-typical pattern and a male typical pattern."

    • A woman with CAH was banned from competing in the Olympic Games as a woman. Do you agree with this decision?
    • Do you think a person with male (XY) chromosomes but suffering from Testicular Feminising Syndrome (see Carlson) should be allowed to enter women's events?
    • How would you decide whether a person should be allowed to compete in mens' or women's events?
    • What tests would you employ? Would you base your testing on a person's sex or gender?

    According to a nature view of psychosexual differentiation, prenatal exposure to androgen could influence the development of gender identity - the feeling an individual has of being a man or a woman. In contrast the nurture position holds that we are psychosexually neutral at birth and that socialization is responsible for the development of gender identity.

    In 1972 Money and Ehrhardt reported the case of a 7 month old baby boy - one of a pair of twins - born in 1963 whose penis was removed after an operation for circumcision damaged the child's penis. At 22 months old the child was surgically reassigned as a girl and brought up according to the prevailing view at the time that we are psychosexually neutral at birth. This case entered the textbooks and informed medical opinion for several decades because Money reported that the child had adapted well as a girl. But long term follow up of this case by Milton Diamond paints a very different picture of the success of this application of the nature theory of psychosexual differentiation.

    Here is a summary of Diamond and Sigmundson's (1997) paper:

    Dr Milton Diamond, Hawaii University

    "This article is a long-term follow-up to a classic case reported in pediatric, psychiatric, and sexological literature. The penis of an XY individual was accidentally ablated and he was subsequently raised as a female. Initially this individual was described as developing into a normally functioning female. The individual, however, was later found to reject this sex of rearing, switched at puberty to living as a male, and has successfully lived as such from that time to the present. The standard in instances of extensive penile damage to infants is to recommend rearing the male as a female. Subsequent cases should, however, be managed in light of this new evidence."

    Here is a newspaper account of the case:

    The man's life history is told as a cautionary tale by Milton Diamond, a sexologist at Hawaii University in Archives of Paediatric Adolescent Medicine. He says that it is the first long-term follow-up of a male with the normal allotment of XY chromosomes who was raised as a female.

    Dr Diamond says that the problems for "John" began when he was eight months old, in 1963. An accident during circumcision left him without a penis. His parents took him to Johns Hopkins University in Baltimore, Maryland, where experts said that the best thing would be to raise him as a girl.

    His testicles were surgically removed and an artifical vagina created, as is done in sex-change operations. John became Joan.

    The result, says Dr Diamond, has often been extolled as the classic demonstration of how the environment can override nature in forming gender identity. In fact, he says, it was nothing of the sort it was a disaster.

    Despite being raised as a girl, Joan never felt happy. At 12, she was given oestrogen therapy to complete the conversion to a woman. She grew breasts, but was never accepted by other girls, nor felt comfortable as a woman.

    At 14, she rebelled, confessing to her doctor: "I suspected I was a boy since the second grade." She was eventually given a mastectomy to remove the breasts and was given male hormones. At the age of 25, now John once more, he married a woman who already had children.

    Dr Diamond says that the case history has implications for any child born with ambiguous sexuality. "Keep your knife away," he says. "Let the kids make a decision when they get older."

    Michael Bailey, a psychologist at Northwestern University, Illinois, told Science Now, a daily science news service run by Science magazine, that the case was heralded by many as the pinnacle of proof that psycho-social factors could override biological factors in determining gender.

    Textbooks continued to claim that Joan made a successful adjustment, in spite of contradictory evidence. Dr Diamond's report, says Dr Bailey, "suggests that, if anything, how you're reared matters little".

    (Text extract from The Times, March 15 1997, by Nigel Hawkes. Pictures from "The boy who was turned into a girl", Horizon, BBC, December 2000)

    Sorting it out

    Here&rsquos how it works: Let&rsquos say that you and your partner each come to your relationship with a set of favorite family recipes. You may contribute a blue-ribbon chili recipe to the table, and your significant other may bring a killer lemon meringue pie. But it&rsquos not just two recipes, it&rsquos hundreds, maybe thousands. Some on index cards, some in books, some on torn-up shreds of cocktail napkins. So what do you do with all these cranberry-mold recipes? Stuff each and every one of them in the kitchen drawer. Now it&rsquos hard to sift through them, you don&rsquot have access to many of them, and you really can&rsquot find what you want. Unless&mdashyou knew there was an &ldquounless&rdquo coming&mdashyou get them organized, say, by sticking hot pink notes on the recipes you really want to access quickly. You tag your favorite recipes, so you can quickly search, find, and put them into action.

    Genes are like recipes. They&rsquore instructions to build something. Both mom and dad contribute a copy of their entire recipe book to their offspring, but for many genes, only one copy of each recipe will be used by the baby. Mom and dad have the same recipes (one for eye color, one for hair color, and so on), except they may have slightly different versions of those recipes these are called alleles.

    For example, eye genes are either brown or blue or green, etc. For such genes, you express only the gene from your mom or dad&mdashthat is, only one copy is active, but not both. In some cases, neither copy will need to be expressed: Eye color only matters to eye cells a liver cell doesn&rsquot need either mom&rsquos or dad&rsquos eye-color gene to be cranking away. So how does a cell turn off the 24,999 genes it doesn&rsquot need and turn on the few it does?

    Every cell&mdashand there are around 200 different types in the body&mdashneeds to know which few genes are relevant to it, and, of those genes, whether mom&rsquos or dad&rsquos will be expressed. As with the kitchen drawer full of recipes, the genes alone are useless unless there&rsquos a way for your body to find what you need, when you need it.

    Mutations in the AR gene cause androgen insensitivity syndrome. This gene provides instructions for making a protein called an androgen receptor. Androgen receptors allow cells to respond to androgens, which are hormones (such as testosterone ) that direct male sexual development. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive. Mutations in the AR gene prevent androgen receptors from working properly, which makes cells less responsive to androgens or prevents cells from using these hormones at all. Depending on the level of androgen insensitivity, an affected person's sex characteristics can vary from mostly female to mostly male.

    Learn more about the gene associated with Androgen insensitivity syndrome

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    &ldquoAs a queer person and a geneticist, I struggle to understand the motivations behind a genome-wide association study for non-heterosexual behavior,&rdquo Joseph Vitti, a postdoctoral researcher at the Broad Institute, wrote on its blog, adding, &ldquoI have yet to see a compelling argument that the potential benefits of this study outweigh its potential harms&hellip [T]he results presented not only oversimplify the question of biological causality, but also threaten direct damage by perpetuating the stereotype of LGBTQIA+ people as imprudent, while also likening same-sex attraction to a medical or psychological disorder.&rdquo

    Geneticist Andrea Ganna of the Broad Institute. Andrea Ganna

    Moreover, a website called The American Conservative posted an article entitled &ldquoNot Born This Way After All?&rdquo which wondered, skeptically: If the study proves that homosexuality is related to the environment, above all, and not to heredity &ndash why isn&rsquot it right and proper, in scientific terms, to allow those who so desire to undergo treatment in order to reduce their same-sex desires, which have now been shown not to be genetic?

    That, however, is a simplistic reading of the study&rsquos findings. According to Michael Bailey, a professor of psychology at Northwestern University in Illinois, who was not involved in the study but has been conducting research on sexual orientation for 30 years, &ldquoIt&rsquos very important to understand that &lsquoenvironment&rsquo does not simply refer to social surroundings, like what your parents teach you and what kids you know, trauma and so on&hellip there&rsquos also a biological environment that begins right after conception.&rdquo

    Three years ago, Bailey and several colleagues published a survey of all the studies and professional literature in the field. &ldquoThe best studies have shown that genes are probably important but not overwhelmingly important,&rdquo he tells Haaretz. &ldquoWe estimated in our 2016 review&hellip that 30 percent of the variation in sexual orientation is due to genetic variations.&rdquo It may be this finding that led him to conclude that &ldquoit is the biological environment that is mostly important.&rdquo Bailey is convinced that men are born with their sexual orientation and that it is not subsequently acquired at any stage. He notes that there are &ldquoseveral cases, I think there are seven throughout the professional literature, in which a baby boy was changed into a girl for medical reasons and was raised as a girl. When you follow these individuals through adulthood, you find that they are attracted to women and not to men.&rdquo

    In Bailey&rsquos view, the best example of how biological-environmental factors can influence sexual orientation is the &ldquofraternal birth order effect.&rdquo The phenomenon, whose existence is &ldquowell established,&rdquo he says, shows that &ldquothe more older brothers a man has, the more likely he is to be homosexual.&rdquo In practice, every older biological brother increases the probability that the youngest brother will be gay by about 33 percent. Thus, if the probability that a man with no older brothers will be gay is 2 percent, one older brother will increase the probability to 2.6 percent, and a second, third and fourth brother to 3.5 percent, 4.6 percent and 6 percent, respectively. What&rsquos not yet clear is the reason for this.

    &ldquoIn my mind,&rdquo Bailey suggests, &ldquothe best hypothesis as to why this happens is that a mother&rsquos immune system becomes increasingly active and produces antibodies against male proteins over successive births.&rdquo

    Fingers and hands

    Behind this hypothesis is one of the most influential figures in the field, American-Canadian clinical psychologist and sexologist Ray Milton Blanchard. He was also among those who linked the fraternal birth order effect to another phenomenon of interest to scientists: the connection between being left-handed and having a same-sex orientation. The most extensive study in this regard was conducted in 2000, incorporating 20 different studies involving 7,000 gay male and female subjects and 16,000 heterosexual ones. It was found that gay men were 34 percent more likely to be left-handed. The situation was more extreme among lesbians: They were seen to have a 91 percent greater chance than straight women of writing with their left hand.

    As a result, six years later, a research team led by Blanchard argued that the fraternal birth-order effect is relevant only among right-handed men. The reason is that, in any case, left-handed men who don&rsquot have older brothers already have a greater likelihood of being gay than right-handed men with such siblings.

    A person&rsquos dominant hand turns out to be significant in another sense as well. An article published two years ago (about a study in which all the subjects had taken part in a gay pride parade in Toronto) found a connection between that hand and the gay person&rsquos &ldquorole in bed&rdquo: that is, the proportion of left-handed gays who defined their sexual behavior as passive or versatile (i.e., sometimes passive, sometimes not) was significantly higher than among those who described themselves as actives &ndash who clearly tended to be right-handed.

    A gay pride parade in Toronto, Canada. Geoff Robins / AFP

    In research conducted over the years on the subject of the connection between sexual orientation and other attributes of the body, the hand holds a place of honor. But while Blanchard developed his theory on the basis of the whole hand, sometimes a few fingers are also enough: two, to be exact. In his 1998 study, British biologist John Manning confirmed a relatively old hypothesis, first put forward in Germany almost 150 years ago. Its gist is that the proportion between the length of index and ring fingers is, typically, different in men and women. Manning found that this phenomenon was detectable as early as age 2, which led to the observation that its source lies in the differences in testosterone and estrogen levels that already exist in the womb &ndash hereinafter: a biological-environmental factor.

    Manning did not emphasize the element of sexual orientation in the two books and over 60 articles he wrote on this subject, but in the two decades that have elapsed since his study, more than 1,400 papers have been written on the ratio between the length of the second and fourth fingers (known as 2D:4D) and the connection between it and the level of risk of contracting certain diseases, as well as personality traits, cognitive and athletic abilities &ndash and sexual orientation.

    One such study, published in 2010, maintained that straight and lesbian women are differentiated by the ratio between the length of the index and ring fingers, with lesbians tending to show a more &ldquomasculine&rdquo ratio &ndash i.e., closer to the average difference between the length of the fingers, among men. However, no such differences were found between gay and straight men.

    Last year a team of scientists led by a British psychologist measured the fingers of 18 pairs of identical female twins, one lesbian, the other straight. Overall, differences in proportion were documented only in the lesbians and only in their left hand, and were comparable to the situation among men. This fact, the team concluded, could indicate a heightened exposure to testosterone in the womb &ndash but their study was based on a very small sample and drew much criticism. The critics charged that the conclusion was based on an overly simple means of measurement: of the way only two variables impacted each other. And, they added to bolster their argument, findings of studies involving those fingers have not been replicated in scientific experiments.

    The field of &ldquogay science&rdquo has been on a roll in recent years, but has a far longer history. Its modern phase dates to the early 1990s, when scientists began to publish increasing numbers of studies arguing that sexual orientation has a biological component. A leading scientist in this field is British-American neurobiologist Simon LeVay, who in 1990 performed autopsies on the bodies of 41 people: 19 gay men, 16 straight men and nine women. He discovered that the brain cells known as INAH-3 among the deceased gay men were relatively small, and closer in size to those of women than to heterosexual males.

    &ldquoIn 1991,&rdquo LeVay told Haaretz in a phone conversation, &ldquoI published a study that got a lot of media attention, related to my observation that there was a region inside the hypothalamus that was different in size between men and women, and also between gay and straight men&hellip My additional finding was the difference in size between gay and straight men in this region inside the hypothalamus that is involved in the regulation of sexual behavior.&rdquo

    Adds LeVay, &ldquoMy general feeling is that there are certainly strong biological influences on people&rsquos sexual orientation, but we can&rsquot say everything is genetic.&rdquo

    In the spirit of the period, and in light of the AIDS epidemic at the time, LeVay tried to be as cautious as possible about his conclusions. &ldquoIt&rsquos important to stress what I didn&rsquot find,&rdquo he said in an interview to Discover magazine, in 1994. &ldquoI did not prove that homosexuality is genetic, or find a genetic cause for being gay. I didn&rsquot show that gay men are &lsquoborn that way,&rsquo [which is] the most common mistake people make in interpreting my work.&rdquo

    Three decades after publishing his study, he still thinks media coverage is doing an injustice to research &ndash even if it&rsquos not his. &ldquoI&rsquove seen some headlines saying, basically, that this study [i.e., that of Ganna and his associates] shows it&rsquos not genetic, or that are no gay genes, or something like that and, of course, it&rsquos not what the study shows at all.&rdquo

    In recent decades, scientific research (on men and women alike) in this realm has relied on an additional field: molecular genetics. The pioneer is geneticist Dean Hamer, who in 1993 conducted the first study of its kind.

    &ldquoWe noticed that being gay, for males, tended to pass down through the mother&rsquos side of the family,&rdquo he told Haaretz. &ldquoAnd that is characteristic in genetics of something on the X chromosome &ndash because males get their X chromosomes from their moms&hellip That led us to look in families where there were gay brothers, to see if they shared anything on the X chromosome.&rdquo

    And thus, recalls Hamer, he and his team discovered Xq28: a genetic marker that plays a part in determining whether a person will be heterosexual or gay. He emphasizes that this is &ldquoa factor, it&rsquos not the factor and actually, overall, it&rsquos not even the most important factor.&rdquo He adds, &ldquoWhat&rsquos good about genetic studies, is that you know that whatever you find is a causal factor, because &ndash of course &ndash people are born with their genes, and it&rsquos not something that changes over time.&rdquo

    LeVay, he explains, &ldquois looking directly at the brain, and we&rsquore looking at what we think is building the brain and genes.&rdquo Yet, &ldquoit&rsquos very difficult to know whether one was born with a brain like that, or whether that brain developed that way because of your behavior &ndash the causality is rather unknown.&rdquo

    At the same time, Hamer adds, &ldquoThat doesn&rsquot mean there aren&rsquot specific pathways, because there has to be some sort of a pathway in the brain that controls sexual orientation. We know, for example, that the reason you become a male or a female is very simple: If you have a certain gene on the Y chromosome, you will produce male hormones, and if you have those you make a penis and scrotum and you become male.&rdquo Accordingly, &ldquoThere&rsquos probably some pathway in the brain that does same thing for sexual orientation, but we&rsquore not going to discover it from genetics&hellip The answer will probably emerge from some sort of very sophisticated brain and developmental studies.&rdquo

    Illustration Rotem Teplow

    For 35 years, Hamer accumulated experience as a scientist at the National Institutes of Health in Bethesda, Maryland. That period is behind him. He doffed the white coat and now lives in Hawaii, where he makes films. But even if he&rsquos no longer occupied with research, it still occupies him.

    Hamer: &ldquoBack in the 1990s, I, along with all the scientists involved, believed that if we did good genetic studies we&rsquod find the important genes. For example, we&rsquoll find a gene that is responsible for the production of testosterone, and if its functioning was low, it would be possible to say that this is the cause of homosexuality in a particular person&hellip. But it turns out that it doesn&rsquot work that way. For every mental trait that has been studied&hellip everything you can imagine in the brain, for every single trait, there&rsquos a [vast number of] genes&rdquo &ndash not to mention a host of complex societal and environmental factors.

    For his part, Hamer has much praise for the Broad Institute study: &ldquoThe new GWAS study is really important, because for the very first time they used a huge sample and they mapped every inch of the genome. And this has never been done before. All the other studies were much smaller, or used many fewer genetic markers.&rdquo But he also demurs: &ldquoWhat&rsquos very important is to look at what they actually analyzed. They didn&rsquot analyze people who were gay or lesbian, but anyone who had one single same-sex experience, which is quite different. They were measuring something more like openness to sexual experimentation.&rdquo

    As Hamer sees it, &ldquoIf you look for those five markers, or even just the three strongest markers, they are not necessarily found in people who actually identify as gay or lesbian. If you take people who are gay, like me, and look for those markers &ndash they&rsquore not significantly there.&rdquo

    Hamer thinks that the whole field is lagging behind because of insufficient research, owing to the stigmas that plague the subject. &ldquoI don&rsquot think sexuality is any more complicated than many other areas of human personality and individual differences,&rdquo he observes, noting, &ldquoWe formally established that male sexuality is something that is deeply ingrained in people, it&rsquos not any sort of choice really. It starts really early in life, and it has a major biological component to it. But, how it works? What the biological component is? We&rsquore completely unaware and don&rsquot know anything, and we barely know more than we did 25 years ago, or in the 1940s, when Kinsey did his work, to be honest.&rdquo

    Hamer was referring to biologist Alfred Kinsey, who in 1948 stunned the American public with his book, &ldquoSexual Behavior in the Human Male,&rdquo which addressed previously taboo subjects, and challenged the traditional beliefs and existing knowledge about human sexuality. Kinsey had conducted a survey of men, which found that 37 percent of his subjects said they had undergone a homosexual experience of some kind, and 10 percent said they had been exclusively gay for three years of their adult life &ndash a statistic which to this day is generally said to represent the proportion of people engaging in same-sex behavior.

    At the same time, subsequent studies reveal that the percentage of people who define themselves as &ldquoexclusively&rdquo homosexual is far lower, though it fluctuates from one article to the next. For example, a 2011 survey of nine different studies on the subject revealed that approximately 3.5 percent of Americans identify themselves as gays, lesbians or bisexuals. A poll involving 1,000 Jewish Israelis in 2012 found that 11.3 percent of the male respondents and 15.2 percent of the female ones said they felt an attraction to members of the same sex. However, only 8.2 percent of the men categorized themselves as gay or bisexual, while 4.8 percent of the women said they were lesbian or bisexual.

    For his part, Ganna, of the Broad Institute, understands some of the criticism of his research. &ldquoWhat we studied is not related directly to the biology, but to extended environmental factors related to it. It&rsquos not about our sample size &ndash once you have a lot of individuals, you can capture very small effects. But are these directly influencing same-sex behavior, or other things related to this topic? As a medical example, think about a study that looks for associations between genetic markers and lung cancer. In that example, what we found are genetic variants regarding how much you smoke, which is related to lung cancer.&rdquo

    One of the lessons, and one of the most interesting points arising from the study has to do, says Ganna, with the mode of measurement that had been in use since 1948, when Kinsey&rsquos scale ranked individuals as being between 0 (totally heterosexual) and 6 (totally homosexual).

    Ganna: &ldquoBasically, the tendency is to locate individuals on a continuum. You can supposedly be anywhere between 100 percent heterosexual to 100 percent homosexual, which implies that the more you&rsquore homosexual, the less you&rsquore heterosexual, and vice versa. We show that this assumption actually doesn&rsquot hold water: When we look at the genetic data, it&rsquos not that straightforward, there&rsquos no simple continuum of sexuality.&rdquo

    So, actually, you are refuting the Kinsey scale?

    Ganna: &ldquoThat&rsquos exactly one of our conclusions. What we&rsquore now doing is, rather than asking people to put themselves on a scale somewhere between being exclusively heterosexual or exclusively homosexual, we ask them how much they&rsquore attracted to men and women. You could be attracted to either of them, very attracted to both of them &ndash or to one more than the other. And that information will be crossmatched with genetic markers.&rdquo

    In the final analysis, he adds, &ldquoWe showed that this is just another natural human variation. Sexual orientation, similar to many other behavioral traits, is complicated and is composed of different factors. The interesting thing is how genetics and environment work together. If you think about how much more prevalent same-sex behavior has become lately, people engage in it more than in the past. And that&rsquos clearly not because our genetics are changing. It&rsquos because of the environment, because society is becoming more open and laws are changing.&rdquo

    Alfred Kinsey. Keystone Features / Getty Images

    Further research should focus on the relationship between environmental factors and genetics, Ganna says, and on how they interact. &ldquoIt&rsquos somewhat misleading to think of nature and nurture as separate aspects they both contribute. So, it would be wrong to say that you can use only DNA to predict if someone will engage in same-sex behavior, but you also can&rsquot say it&rsquos simply a [matter of] choice.&rdquo

    In summary, he says, &ldquoI think that the more people who will understand that there are genetic and environmental components to sexual behavior, the better &ndash and this is a message that goes beyond just sexuality.&rdquo

    Choice and lifestyle

    However, the relationship between science and the environment, and particularly the people living in it, is a complicated one. &ldquoThe subject definitely should be studied, but the social aspect of it is problematic,&rdquo says LeVay, the neurobiologist. &ldquoI am gay myself, and I feel strongly that gay people should be valued and accepted into society, regardless of what caused their sexual orientation. I don&rsquot think it&rsquos vital for gay liberation to prove that &lsquogay people can&rsquot help but be gay&rsquo &ndash there are plenty of other reasons [for accepting them], including basic human rights.&rdquo

    At the same time, he adds, &ldquothis issue is socially relevant, because of traditional notions that see same-sex relations as a choice, a &lsquolifestyle&rsquo or sinful behavior.&rdquo

    In recent years, &ldquothere have been many studies showing that people&rsquos attitudes toward homosexuality are closely tied to their beliefs about what makes people gay,&rdquo says LeVay, citing a survey that showed there was a high probability that people who think homosexuality is a choice will object to a gay person being their children&rsquos teacher &ndash which in a way might make sense, he adds: &ldquoIf you think being gay is something infectious, socially contagious, and you didn&rsquot want your kid to be gay, then you wouldn&rsquot want their teacher to be gay . It follows that demonstrating that biological factors are involved, helps counter those ideas. Still, I&rsquom a bit ambivalent about the use of this type of research as some sort of a political weapon in the struggle for gay rights.&rdquo

    The Broad Institute study contains a reminder of the problems and stigmas that still exist with regard to the LGBTQ community. One of the parameters it considers are genetic correlations between genes that are ascribed to homosexuality, and certain psychological problems.

    Bailey, the psychologist: &ldquoOne thing that was perceived as controversial, was to look for &ndash and find &ndash a genetic overlap between homosexual sex genes and genes associated with depression. It&rsquos not the same as saying all people who engage in homosexual sex are depressed for genetic reasons, but it&rsquos also not something that can be easily ignored. There are assumptions that the higher rates of depression among gay men and lesbians is due to the way they are mistreated by society, but the evidence for that is not so overwhelming. There is also the fact, for example, that you have as high a rate of depression among homosexual men in the Netherlands, which is very tolerant, as you have in some less tolerant places, like the United States.&rdquo

    Ganna, for his part, tries to soften that criticism: &ldquoEven if we see genetic overlap, or correlation, it is not set in stone that we&rsquove found a biological mechanism that causes depression and same-sex behavior,&rdquo he says. &ldquoThere are many explanations for why this one genetic marker is associated with both things. But finding these correlations help us study human traits in general.&rdquo

    In the meantime, there is a price to be paid for conducting research in this realm, which all those involved must be aware of. Reminders of this abound, and are almost routine. In some cases what&rsquos at stake is not even a groundbreaking study or one of tremendous scientific importance. In 2017, for example, two researchers from Stanford published an article stating that &ldquogay men are predicted to have smaller jaws and chins, slimmer eyebrows, longer noses, and larger foreheads the opposite should be true for lesbians.&rdquo In the next stage, they created a facial-recognition program with the aid of more than 14,000 images taken from a singles site of straights and LGBTQs. The program was able to distinguish between gays and lesbians and heterosexuals with an accuracy of 81 percent for men and 71 percent for women, in contrast to an average rate of successful human guesses of 61 percent and 54 percent, respectively. Even though the program achieved relatively impressive results, the study as such drew widespread criticism &ndash not unusual for researchers engaged in such studies.

    The Stanford &ldquogays identification&rdquo program may be an extreme example, in this respect, but it&rsquos also a byproduct of the considerable surge in studies in this field, a trend that began in the early 1990s. Together with the scientific community, media interest in the subject of same-sex orientation and its causes has contributed substantially to transmitting messages and shaping public opinion.

    In the United States, this can be seen in a series of polls conducted by Gallup, Inc. The first one, conducted in 1977, found that only 13 percent of the respondents believed that homosexuality is an innate tendency, while 56 percent attributed it to environmental factors. This approach remained largely constant until the period between 1989 and 1996, when the rate of those supporting the innate thesis leaped from 19 percent to 31 percent by 2001, it stood at 40 percent. Almost a decade and a half later, the annual poll produced, for the first time, a larger proportion who agreed with the innate argument. The latest survey, from the end of last year, showed this trend continuing: More than half of the American public believes that gay people are born with their sexual orientation, whereas only 30 percent attribute it to environmental factors (10 percent said both factors play a part, 4 percent cited other factors and 6 percent said they weren&rsquot sure).

    Changes in the perceptions of the origins of sexual orientation are having a pronounced effect on the struggle LGBTQ individuals are waging for equal rights. The latest Gallup poll shows that an absolutely majority (88 percent) of those who believe that homosexuality is an innate trait also support legitimizing same-sex marriages. In contrast, most of those who see this orientation as being environmentally driven (61 percent) are against.

    &ldquoWhen it comes to public opinion, which is very important, the &lsquoborn this way&rsquo idea has been really resonant and has had a very positive impact on society,&rdquo Hamer maintains. &ldquoPublic opinion polls asked people whether they think [gays] were born this way or not, and we know that believing that homosexuality is innate correlates with having positive feelings toward gay rights. Overall, it&rsquos been important in educating the public about who we are, as gay people.&rdquo

    Such messages are reaching Israel as well. A poll conducted by the Dialog Institute for Haaretz at the end of 2013 found that 70 percent of those questioned favored full rights for same-sex couples, while 64 percent specifically backed their right to surrogacy. However, two polls conducted in the wake of the surrogacy law protest in July 2018 presented slightly lower numbers: About 57 percent of respondents expressed support for the right of same-sex male couples to surrogacy.

    These polls did not ask Israelis whether they believe the origin of same-sex orientation is innate or environmental. If you ask Bailey, though, that doesn&rsquot really matter.

    &ldquoI&rsquove gone to great lengths to try to persuade people not to base equal rights for gay people on the causal hypothesis,&rdquo he says. &ldquoIt&rsquos a terrible idea to say gay people should have equal rights because they were born that way. It&rsquos terrible in part because some criminals might be born that way, and you don&rsquot want to them to have the same rights. Being gay doesn&rsquot harm anybody, other than people who are close-minded and easily offended. Preventing people from expressing their homosexuality is quite destructive for them. That&rsquos true whether gay people are born that way or not.&rdquo

    Deepening the nature v. nurture debate: How hormones impact development in the womb is often most key

    One of the longest-running debates in the realm of child development is the question of whether we are the result of our environment or our genetics. Reality, however, is more complex and more intriguing.

    The oversimplification of this matter, which has been a major topic of debate and scientific inquiry among psychologists, physicians, and scientists of all stripes since the term nature vs. nurture was coined by Francis Galton in 1869, does not give due consideration to that time when the two are inextricably intertwined: that crucial forty weeks, give or take, during which a human grows from fertilized egg to embryo to fetus. And there is now research suggesting a third manner of passing on genetics to offspring: the control of genetic expression and hormonal imprinting set in motion by exposure to hormones during gestation.

    The research in this arena is ongoing, but it is clear that hormones released during gestation appear to affect the development of the fetal brain in a number of ways.

    It is common knowledge that deficiencies of nutrients in a pregnant person’s diet, pathogens, medications, and other outside influences can have a teratogenic effect. For example, a medication used to treat severe cases of cystic acne, Acutane (retinoic acid), is known to cause birth defects through mutation of the SSH Gene(Sonic Hedgehog Gene).

    What is not well known outside the scientific community is that factors within the gestational partnership between fetus and parent, in particular the balance of hormones released into the mother’s bloodstream, also have a profound effect on the expression of genes within the placenta and the fetal brain, affecting intelligence, mental health, social and developmental disorder manifestation, brain size and structure, susceptibility to stress and sensitivity of the fight or flight response, and hormonal imprinting, to name a few.

    The mother’s hormones appear to have a programming effect on the fetal brain through the phenomenon of hormonal imprinting. The exposure of the developing brain to varying levels of particular hormones will permanently set how responsive the fetus’s hormone receptors are for the rest of their lives. Two such examples of hormonal imprinting involve oxytocin and cortisol.

    Exposure to cortisol while in utero appears to affect the formation of the stress-response axis, responsible for how the offspring reacts when exposed to stressful stimuli. But it isn’t as simple as a dose-response system or the negative effect of teratogens(an element that causing malformations of an embryo or fetus by way of exposure).

    When examining cortisol exposure during pregnancy, it appears that timing of exposure, amount of exposure, and the slope of increase in exposure(cortisol exposure naturally increases over the course of a pregnancy) all contribute to the final outcome. What we find is a U-shaped curve where the lowest and highest levels of cortisol exposure in pregnancy are associated with negative outcomes, including exaggerated stress response in childhood and impaired brain development.

    As evidenced by a study published in 2010 involving 125 full term infants whose mothers were tested for cortisol levels and surveyed for psychological states five times during pregnancy, early exposure to elevated cortisol levels negatively impact offspring while late exposure to high cortisol has a salutary effect. The infants in the study exposed to elevated cortisol early in gestation showed slower growth and lower scores in mental development when tested at 12 months with the Bayley Scale of Infant Development (BSID) whereas infants exposed to higher cortisol during late gestation showed faster development and higher mental development scores on the BSID.

    It also appears that a steeper increase in cortisol across the course of a pregnancy, starting with a lower level in the first trimester and ending with a higher level in the last few weeks, improves outcomes evidenced by faster mental development over the first year and resulting in higher intelligence scores at a year. Only infants with a moderate average exposure (lack of either high exposure in the first 18 weeks, no abnormally high exposure at any recorded time and a moderate level recorded overall) to cortisol do not exhibit an exaggerated stress response in infancy. A study conducted in India, in which 133 pregnant women were evaluated for depression before and after birth using the Kessler scale and the Edinburgh Postnatal Depression Scale and then following up with 58 of their infants, looking for a connection between cortisol secretion during pregnancy and exaggerated stress responses in childhood found that two-month-old infants tested for salivary cortisol levels following immunization showed exaggerated responses to immunization if they had been exposed to very high or very low levels of cortisol during pregnancy.

    The implications of these findings are many and in need of further research, but thus far it appears that increasing cortisol exposure once the developing child has passed the vulnerable first trimester of development provides a blueprint within the brain for future stress responses in life — stress responses that should approximate those needed for survival in the world the parents are living in. It stands to reason that a child born into a high-stress world (threat of natural disaster, war, or predators) would need a sensitive and rapid stress reaction to survive. In theory, by exposing a fetus to high levels of cortisol early in pregnancy, we create a child built for extreme reactions to meet an extreme world. When the developing child is exposed to unusually low levels of cortisol in the womb, their stress-response axis may be unable to properly process stressors (cortisol) when tested in infancy, this is evidenced by an exaggerated response to stressors, similar to their high cortisol exposure counterparts. This line of thinking leads us to the hypothesis that there are either ideal levels and timing for cortisol exposure in the developing infant, or, at least, a range of acceptable levels. Exposure above or below that range, or during crucial time frames, may result in negative outcomes.

    Aside from the effect on the stress-response-axis, cortisol increases during development in some studies show a decrease in synaptogenesis, hippocampal weight, and fewer glucocorticoid receptors in both the amygdala and the hippocampus. These changes are associated with poorer memory and decreased ability to learn, and all of these changes are found in conjunction with changes in gene expression within the placenta.

    The Oxytocin system is another area that is being researched for its significance to human behavior. Oxytocin has been known as “the love hormone” but more accurately is responsible for setting appropriate social interactions in place — including the urge to nurture and protect young, mate and defend one’s mate, and socialize or compete with same-sex comrades in heterosexuals.

    The oxytocin system is not only affected by the administration of exogenous oxytocin and oxytocin receptor antagonists but also by levels of steroid hormones including progesterone, testosterone, and estrogen. As with cortisol, these exposures during pregnancy and early postpartum result in hormonal imprinting that will guide future behaviors. These behavioral changes, or, rather, preset baselines for behaviors, result from changes in the fetal brain by way of gene expression, neuron function, cell morphology (shape and appearance of cells), and axonal guidance (process by which neurons send out axons to reach their targets).

    Furthermore, a study on rats showed that a single dose of oxytocin at birth reduced the turnover of dopamine and serotonin in the brain of the rats at 4 months of age. These findings are significant considering that a number of conditions of the mind including autism and schizophrenia appear to be related to disturbances of the serotonin and dopamine systems.The hormonal imprinting of the oxytocin system during gestation appears to be responsible for many future outcomes, including anxiety levels, prosocial behaviors, addictive tendencies, parenting, pair-bonding and sexual behavior. When oxytocin receptor antagonists are administered we see changes in what we believe are oxytocin fueled behaviors. In some species we witness a decrease in aggression and competition for mates and an increase in anxiety. With application of oxytocin, we witness increases in mating behaviors, aggression, attentiveness to young, pair-bonding, and in some species (mice, prairie voles, and pigs), a decrease in same-sex socialization and an increase in competitiveness and in others the opposite.

    The big question here is: What does the idea that hormonal fluctuations during gestation shape the genetic expression, behaviors, and actual brain structures of our offspring mean? First and foremost, it means that more research needs to be conducted to learn about hormonal imprinting and its effects on lifelong health before we even consider further tampering with the oxytocin systems in our offspring through interventions like the induction of labor with oxytocin receptor antagonists, including Pitocin (exogenous oxytocin), as well as exercising caution when determining whether to introduce interventions that increase cortisol exposure.

    At the same time, cortisol and oxytocin are only two of many hormones that a fetus is exposed to during gestation, and we would do well to further examine the effects of them all.

    When considering the manner in which mental and behavioral health conditions are passed on from parent to offspring, hormonal imprinting must be looked at as a significant variable at play and researched as a possible means to prevent the inheritance of mental illness. If extreme hormonal fluctuations in the mother can be prevented and even levels of specific hormones manipulated to meet a range of ideal or normal exposure, it may be possible to stop the genetic predisposition to disadvantageous mental disorders that might be hard-wired during gestation.

    In the meantime, it is safe to say that measures should be taken to decrease stress and improve familial and societal supports during childbearing to ensure the next generation has the fullest potential to thrive. Should we reach a point where we become able to gestate our progeny outside of a human body, using an artificial womb through ectogenesis, we must take great care in controlling for the timing, frequency, and level of exposure to hormones for developing and imprinting optimal health of body and mind.

    Cherrie Newman is a writer and student of human reproduction with the Ancient Art Midwifery Institute. She is the author of a science fiction novel series entitled Progeny under the pseudonym CL Fors. Follow her on her blog or on Twitter @ clfors.

    Prenatal Genetic Tests

    Doctors also can use prenatal tests to look for signs that your baby is at risk for certain genetic disorders or birth defects. You don’t have to have these tests, but your doctor may suggest some to make sure your baby is healthy.


    They’re especially important for women who have a higher risk of having a baby with a birth defect or a genetic problem.This is you if you:

    • Are over age 35
    • Have had a premature baby or a baby with a birth defect before
    • Have a genetic disorder or one that runs in your family or the other parent’s family
    • Have a medical condition like diabetes, high blood pressure, a seizure disorder, or an autoimmune disorder such as lupus
    • Have had miscarriages or stillborn babies in the past
    • Have had gestational diabetes or preeclampsia when you were pregnant before

    Some prenatal genetic tests are screening tests. They tell you if your baby has a higher risk of having a certain disorder or disease, but they can’t tell you for certain that they’ll be born with it. Other “diagnostic” tests will give you a more definite answer. Usually, you’ll get this kind after you have a positive result on a screening test.

    To start, your doctor may want to test you and the child’s other parent for the genes that cause certain genetic diseases, like cystic fibrosis, Tay-Sachs disease, sickle cell disease, and others. If both of you have a gene for one of these diseases in your DNA, you could pass it on to your baby, even if you don't have the disease itself. The exam is called a carrier test.

    Your doctor can use one or more different screening tests to check your baby for a genetic problem, including:

    Ultrasound. You’ll already have one of these early in your pregnancy to make sure everything is going well. But if you have a high-risk pregnancy, you’ll need this exam more often. Around 11-14 weeks, doctors can use it to look at the back of your baby’s neck. Folds or thick skin there could mean a higher risk of Down syndrome. Your doctor also may take a sample of your blood at the same time.

    Integrated Screening. There are two phases to this test. In the first part, doctors combine the results of the ultrasound looking at your baby’s neck and the blood tests you got at 11-14 weeks. Then, they’ll take a second blood sample between 16-18 weeks. The results measure your baby’s risk for Down syndrome and spina bifida, a spinal cord and brain disorder.


    Sequential Screen. This is similar to integrated screening, but your doctor reviews the results with you right after the first phase at 11-14 weeks. It’s not as accurate as the longer test, but it lets you know your baby’s risk earlier. If the screening finds there may be a problem, your doctor will use more tests to find out for sure. If it doesn’t find a risk, you’ll most likely get the second blood test at 16-18 weeks to be safe.

    Triple or quadruple screening test. Doctors check your blood for hormones and proteins that come from your baby or your placenta, the organ that brings them oxygen and nutrients. The test can look for three different substances (triple screening) or four (quadruple screening). Certain amounts of these mean your baby has a higher chance of having a birth defect or a genetic disease. This test happens in the second trimester, usually at 15 to 20 weeks.

    Cell-free fetal DNA testing. Doctors use this test to find your baby’s DNA in your blood and check it for Down syndrome and two other genetic conditions, trisomy 18 and trisomy 13. You can have this done after 10 weeks of your pregnancy. Doctors don’t recommend it for every woman, usually only those who have a high-risk pregnancy. It’s not available everywhere, and some health insurance policies don’t cover it. Talk to your doctor about whether you need this test.

    UC Berkeley Psychologist Finds Evidence That Male Hormones In The Womb Affect Sexual Orientation

    BERKELEY -- The level of male hormones in the womb can influence an unborn child's future sexual orientation, according to new research from a University of California, Berkeley, professor who used an unusual technique - measuring finger length - to gather evidence.

    Marc Breedlove, professor of psychology, also found that higher levels of these male hormones, or androgens, can create a greater than normal tendency for both males and females to develop a homosexual orientation.

    "There is no gene that forces a person to be straight or gay," said Breedlove, who studies the biology of sexual orientation. "I believe there are many social and psychological, as well as biological, factors that make up sexual preference.

    "Having said that, these data do suggest that there are some people in the world who are gay because of fetal androgen levels."

    Breedlove's findings appear in this week's issue of the journal Nature.

    Breedlove looked at relative finger length because it is influenced by androgen levels in the womb and thus is an approximate measure of fetal androgen levels.

    In most people, the index finger is very slightly shorter than the ring finger, but, at least in the right hand, the difference is accentuated by higher levels of androgens during fetal development. Typically, in women, the two fingers of the right hand are nearly the same length. In men, the index finger is obviously shorter.

    Breedlove collected data on 720 people who attended three San Francisco Bay Area street fairs in the fall of 1999. Using a portable copy machine, his research assistants had subjects lay their hands flat on the machine to record finger lengths. Breedlove also administered a questionnaire that explored birth order and sexual orientation.

    According to the data collected, homosexual women, on average, had a more masculine finger length pattern - an index finger considerably shorter than the ring finger on the right hand - than did heterosexual women.

    ". this suggests that at least some lesbians were exposed to greater levels of fetal androgen than heterosexual women," Breedlove and his colleagues wrote.

    Men had more a complicated pattern: There was no direct relationship between finger length and sexual orientation. However, some gay men did appear, based on their finger lengths, to have been exposed to greater than normal levels of fetal androgens before birth.

    "This calls into question all of our cultural assumptions that gay men are feminine," said Breedlove. He said his findings are consistent with other, very sketchy indications that some gay men are hypermasculinized, having a greater average number of sexual partners in a lifetime than heterosexual men, higher than normal levels of testosterone circulating in the blood, and larger genitalia than heterosexual men.

    Breedlove's findings, combined with other recent research, paint a complicated picture of the role played by fetal androgens in determining sexual orientation.

    Past research by Ray Blanchard of the Clarke Psychiatric Institute in Toronto has found that the more older brothers a boy has, the more likely he is to be gay in adulthood. The UC Berkeley study confirmed this finding, in that gay men had a ratio of 140 brothers to 100 sisters among their older siblings. This is much higher that in the general population, where the ratio is 106 brothers to 100 sisters.

    The UC Berkeley study also found that men with older brothers had a more masculine finger length pattern than men without older brothers. The number of older sisters was unrelated to finger measures in either men or women.

    As indicated by the fingers measured in his study, Breedlove said that each subsequent son is exposed to higher levels of male hormones and that, while most later-born sons are straight, the increased androgen level slightly increases the probability of a male child developing a homosexual orientation.

    "This means," said Breedlove, "that somehow the mother's body remembers how many sons she has had and exposes each successive male fetus to more androgen.

    "It is just mindboggling to think that some men are gay because of the number of boys their mothers had before their own birth. These events must register in the woman's body before an individual is even conceived."

    Still, cautioned Breedlove, biology does not determine sexual orientation. The findings are statistical relationships, which means that many men and women do not fit the pattern.

    "There are plenty of gay men who are first-borns, many straight men with older brothers and many women whose fingers give no clue to their sexual orientation," he said. "This is not a test to be used on your friends and neighbors."


    Ginny - The sex of a baby is determined by whether the egg which is carrying an X-chromosome is fertilised by a sperm carrying another X which will produce a girl or one carrying a Y-chromosome which produces a boy. So, in that sense, it's the sperm that decides the sex of the baby. But what determines which sperm is the first to reach and fertilise that egg or which sperm were even in the mix is a lot more subtle and less well-understood.

    Chris - Because the Y-chromosome is likely smaller than the X, some people have argued that they are less of a weight burden for the sperm to push along when it swims and therefore, the Y ones move a bit faster than the X ones. So, depending on when how you time the exposure let's say, you could have a boy or a girl.

    Ginny - There is actually a bias, I think it's a 51 to 49 ratio (boys to girls) which fits with that idea that the Y-chromosome sperm is slightly faster, but there are other things that can skew that. Studies seem to show that men with lower levels of testosterone are more likely to produce female offspring and those with high levels are more likely to produce male offspring. So for example, they found that men with prostate cancer which is very strongly linked with high testosterone levels tend to have more male than female children. On the other hand, men who have fertility problems due to lower testosterone tend to produce females when they do father a child. There was even a study conducted at the University of Glasgow that showed that males who ran further than 30 miles a week at the time of conception are much more likely to produce females. If you do a lot of exercise, that tends to temporarily deplete testosterone levels. So, if conception happens relatively soon after the run, then they tend to be more likely to produce females whereas people who were doing just a little bit of running didn't show that difference at all. Chris - So the bottom line is.

    Ginny - Low testosterone levels in a male and you're more likely to have girls, but it's very slim differences. Only when you look at hundreds of men proportionally, I don't actually think that going out for a jog beforehand will make you more likely to have a girl.


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