Editing Biology and sexual orientation (section)

=== Fetal development and hormones ===
{{Main|Prenatal hormones and sexual orientation}}
The influence of hormones on the developing fetus has been the most influential causal hypothesis of the development of sexual orientation.<ref name="Bailey_2016" /><ref name="Balthazart_2011">{{cite journal | vauthors = Balthazart J | title = Minireview: Hormones and human sexual orientation | journal = Endocrinology | volume = 152 | issue = 8 | pages = 2937–47 | date = August 2011 | pmid = 21693676 | pmc = 3138231 | doi = 10.1210/en.2011-0277 | author-link = Jacques Balthazart }}</ref> In simple terms, the developing fetal brain begins in a "female" state. Both [[INAH3]] (third interstitial nucleus of the anterior hypothalamus) area on the left side of the hypothalamus, which stores gender preference, and the center area of the bed stria terminalis (BSTc) area on the right side of the hypothalamus, which stores gender identity, are undeveloped and function as female. The action of the SRY gene in the Y-chromosome in the fetus prompts the development of testes, which release testosterone, the primary androgen receptor-activating hormone, to allow testosterone to enter the cells and masculinize the fetus and fetal brain. If a sufficient amount of testosterone is received by INAH3 at 12 weeks following conception, the testosterone stimulates the enlargement of INAH3, which is known to be involved in directing typical male sex behavior, such as attraction to females. If INAH3 does not receive enough testosterone to override the circulating estrogen, it may not grow to the size typically observed in males. Subsequently, INAH3 may function as female or partially female, potentially causing same-sex attraction to males. Although the ''size'' of INAH3 in homosexual men compared to heterosexual men may not be statistically different, homosexual men may have a greater cell ''density'' per unit volume than heterosexual men, though a similar total number of INAH3 neurons.<ref name="Balthazart_2011" />

Studies have shown that INAH3 in [[gay men]] has likely been exposed to lower levels of testosterone in the brain compared to straight men, or had different levels of receptivity to its masculinizing effects, or experienced hormone fluctuations at critical times during fetal development. In women, if INAH3 receives more testosterone than is normal for females, INAH3 may enlarge somewhat or even to the size that is normal for males, increasing the likelihood of same sex attraction.<ref name="Bailey_2016"/> Supporting this are studies of the finger [[digit ratio]] of the right hand, which is a robust marker of prenatal testosterone exposure.{{Disputed inline|date=March 2023}} Lesbians tend to have significantly more masculine digit ratios, a finding which has been replicated in numerous cross-cultural studies.<ref name="Breedlove_2017">{{cite journal | vauthors = Breedlove SM | title = Prenatal Influences on Human Sexual Orientation: Expectations versus Data | journal = Archives of Sexual Behavior | volume = 46 | issue = 6 | pages = 1583–1592 | date = August 2017 | pmid = 28176027 | pmc = 5786378 | doi = 10.1007/s10508-016-0904-2 }}</ref> Controlled experiments in animals, where scientists manipulate exposure to sex hormones during gestation, can also induce lifelong male-typical behavior and mounting in females, and female-typical behavior in males.<ref name="Bailey_2016"/><ref name="Breedlove_2017"/><ref name="Balthazart_2011" /><ref name="Roselli_2018"/>

Maternal immune responses during fetal development are strongly demonstrated as causing male homosexuality and bisexuality.<ref name="Balthazart_2018">{{cite journal | vauthors = Balthazart J | title = Fraternal birth order effect on sexual orientation explained | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 2 | pages = 234–236 | date = January 2018 | pmid = 29259109 | pmc = 5777082 | doi = 10.1073/pnas.1719534115 | bibcode = 2018PNAS..115..234B | doi-access = free }}</ref> Research since the 1990s has demonstrated that as a woman has more sons, there is a higher chance of later born sons having same-sex attraction. During pregnancy, male cells enter a mother's bloodstream, which provoke an immune response to neutralize them. These antibodies are then released on future male fetuses and may neutralize Y-linked antigens, which play a role in brain masculinization, leaving areas of the brain responsible for sexual attraction in the female-typical default position, i.e. expressing attraction to men. Each subsequent son will increase the levels of these antibodies, creating the observed [[fraternal birth order effect]]. Biochemical evidence to support this effect was confirmed in a lab study in 2017, finding that mothers with a gay son, particularly those with older brothers, had heightened levels of antibodies to the NLGN4Y Y-protein than mothers with heterosexual sons.<ref name="Balthazart_2018"/><ref name="Bogaert_2018">{{cite journal | vauthors = Bogaert AF, Skorska MN, Wang C, Gabrie J, MacNeil AJ, Hoffarth MR, VanderLaan DP, Zucker KJ, Blanchard R | display-authors = 6 | title = Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 2 | pages = 302–306 | date = January 2018 | pmid = 29229842 | pmc = 5777026 | doi = 10.1073/pnas.1705895114 | bibcode = 2018PNAS..115..302B | doi-access = free }}</ref> This effect is estimated to account for between 15 and 29% of gay men, while other gay and bisexual men are thought to owe sexual orientation to genetic and hormonal interactions.<ref>{{cite journal | vauthors = Blanchard R | title = Fraternal Birth Order, Family Size, and Male Homosexuality: Meta-Analysis of Studies Spanning 25 Years | journal = Archives of Sexual Behavior | volume = 47 | issue = 1 | pages = 1–15 | date = January 2018 | pmid = 28608293 | doi = 10.1007/s10508-017-1007-4 | s2cid = 10517373}}</ref><ref name="Balthazart_2018"/>

Socialization theories, which were dominant in the 1900s, favored the idea that children were born "undifferentiated" and were socialized into gender roles and sexual orientation. This led to medical experiments in which newborn and infant boys were surgically reassigned into girls after accidents such as botched circumcisions. These males were then reared and raised as females without telling them, but contrary to expectations, this did not make them feminine nor attracted to men. All published cases providing sexual orientation grew up to be strongly attracted to women. The failure of these experiments demonstrate that socialization effects do not induce feminine sexual behavior or psychology in males, and that the organizational effects of hormones on the fetal brain prior to birth have permanent effects. These indicate the primary role of nature, not post-birth nurture, in the development of male sexual orientation.<ref name="Bailey_2016"/>
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|caption=Average volumes of INAH3 in straight and gay men and in women.<ref name="LeVay_2016"/>
{{legend|#1f77b4|Heterosexual (straight) men}}
{{legend|#9467bd|Homosexual (gay) men}}
{{legend|#e377c2|Women}}
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In the brain, the sexually dimorphic nucleus of the preoptic area (SDN-POA) is a key region which differs between males and females in humans and a number of mammals (e.g., sheep/rams, mice, rats), and is caused by sex differences in hormone exposure.<ref name="Bailey_2016" /><ref name="Breedlove_2017"/> Also, the [[INAH 3|INAH-3]] region is bigger in males than in females, and is known to be critical for sexual behavior. Dissection studies found that gay men had significantly smaller INAH-3 than heterosexual men, a shift in the female direction, as first demonstrated by neuroscientist [[Simon LeVay]], which has been replicated.<ref name="Breedlove_2017" /> Dissection studies are rare, however, due to lack of funding and brain samples.<ref name="Bailey_2016" />
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  |type = rect<ref>{{cite journal|first1=Jiang-Ning|last1=Zhou|first2=Michel A.|last2=Hofman|first3=Louis J. G.|last3=Gooren|first4=Dick F.|last4=Swaab|title=A sex difference in the human brain and its relation to transsexuality|journal=Nature|date=November 1995|pages=68–70|volume=378|issue=6552|doi=10.1038/378068a0|pmid=7477289 |bibcode=1995Natur.378...68Z |hdl=20.500.11755/9da6a0a1-f622-44f3-ac4f-fec297a7c6c2|s2cid=4344570 |url=https://pure.knaw.nl/portal/en/publications/a-sex-difference-in-the-human-brain-and-its-relation-to-transsexuality(9da6a0a1-f622-44f3-ac4f-fec297a7c6c2).html |hdl-access=free}}</ref>
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|caption=Average volumes of the equivalent cell group in sheep (oSDN) for heterosexual and homosexual rams and for ewes.<ref name="LeVay_2016" /> Sex differences are formed under the influence of prenatal hormones in utero, rather than acquired after birth.<ref name="Roselli_2018" />
{{legend|#1f77b4|Heterosexually oriented rams}}
{{legend|#9467bd|Homosexually oriented rams}}
{{legend|#e377c2|Ewes (females)}}
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Long-term studies of [[Homosexual behavior in sheep|homosexual behavior in domesticated sheep]] led by Charles Roselli have found that 6-8% of rams have a homosexual preference through their life. Dissection of ram brains also found a similar smaller (feminized) structure in homosexually oriented rams in the brain region equivalent to human SDN, the ovine sexually dimorphic nucleus (oSDN).<ref name="LeVay_2016">{{cite book |url=https://archive.org/details/gaystraightreaso0000leva_e5c2/mode/1up?view=theater |title=Gay, Straight, and the Reason Why: The Science of Sexual Orientation |vauthors=LeVay S |date=2017 |publisher=Oxford University Press |isbn=978-0-19-029739-8 |language=en |chapter= |ol=26246092M |chapter-url= |ol-access=free}}</ref>{{rp|107–110}} The size of the sheep oSDN has also been demonstrated to be formed in utero, rather than postnatally, underscoring the role of prenatal hormones in masculinization of the brain for sexual attraction.<ref name="Roselli_2018">{{cite journal | vauthors = Roselli CE | title = Neurobiology of gender identity and sexual orientation | journal = Journal of Neuroendocrinology | volume = 30 | issue = 7 | pages = e12562 | date = July 2018 | pmid = 29211317 | pmc = 6677266 | doi = 10.1111/jne.12562 }}</ref><ref name="Bailey_2016" />

Other studies in humans have relied on brain imaging technology, such as research led by [[Ivanka Savic]] which compared hemispheres of the brain. This research found that straight men had right hemispheres 2% larger than the left, described as modest but "highly significant difference" by LeVay. In heterosexual women, the two hemispheres were the same size. In gay men, the two hemispheres were also the same size, or sex atypical, while in lesbians, the right hemispheres were slightly larger than the left, indicating a small shift in the male direction.<ref name="LeVay_2016" />{{rp|112}}

A model proposed by evolutionary geneticist William R. Rice argues that a misexpressed epigenetic modifier of testosterone sensitivity or insensitivity that affected development of the brain can explain homosexuality, and can best explain twin discordance.<ref name=":4" /> Rice et al. propose that these epimarks normally canalize sexual development, preventing [[intersex]] conditions in most of the population, but sometimes failing to erase across generations and causing reversed sexual preference.<ref name=":4" /> On grounds of evolutionary plausibility, Gavrilets, Friberg and Rice argue that all mechanisms for exclusive homosexual orientations likely trace back to their epigenetic model.<ref>{{cite journal | vauthors = Gavrilets S, Friberg U, Rice WR | title = Understanding Homosexuality: Moving on from Patterns to Mechanisms | journal = Archives of Sexual Behavior | volume = 47 | issue = 1 | pages = 27–31 | date = January 2018 | pmid = 28986707 | doi = 10.1007/s10508-017-1092-4 | s2cid = 33422845 | url = https://www.gwern.net/docs/psychology/2017-gavrilets.pdf }}</ref> Testing this hypothesis is possible with current stem cell technology.<ref>{{cite journal | vauthors = Rice WR, Friberg U, Gavrilets S | title = Homosexuality via canalized sexual development: a testing protocol for a new epigenetic model | journal = BioEssays | volume = 35 | issue = 9 | pages = 764–70 | date = September 2013 | pmid = 23868698 | pmc = 3840696 | doi = 10.1002/bies.201300033 }}</ref>