I wanted to share a paper that I think some of my readers would be interested in. I wrote this paper for my Physiological Psychology class this past semester. (Warning, some of the information below is dense and technical.)
I have heard many discussion on where homosexuality might come from. Many of these discussions focus around personal experiences and opinions, these kind of discussions, I have found, are a great way to learn and grow. In these discussions, there seems to be a recurring argument around whether a person chooses to be homosexual or whether they are born that way.
For this post, I wanted to provide a summary of what is known about the origins of homosexuality and a little on gender identity, as well as potential new research that is being done around the world in order to discover, biologically, how homosexuality occurs and why it exists. I included references at the bottom if anyone wants to do further research.
Homosexuality: What is Known and The Role of Epigenetics
Over the past few decades more and more research has been done to try to determine the root cause of homosexuality within the animal and human population. . Homosexuality seems to be a very complex and complicated phenomenon because it has been found to have more than one system involved with the development of this phenotype. Research has found differences in brain structure between homosexuals and heterosexuals. These differing brain structures are found to be affected by androgens on the developing prenatal brain. Genetics has also been found to influence the development of homosexuality. The way in which structure, hormones, and genetics interacts is very complex and had mostly been studied separately. An overarching explanation that could unite these different areas of study is epigenetics. It has been found that epigenetics may play a significant role in homosexuality. Not only can epigenetics influence the expression of genes regarding androgen signaling, they can also play a role in determining how certain structures are created in the brain and how the body reacts to certain stressors in utero. This paper seeks to better explain how all this ties together and what we know and what we may need to find out further, based on a review of current research in regards to this topic.
This paper is seeking to compile the evidence that has been found for epigenetic links to homosexuality within the human population, and what is known about the difference between homosexuals and heterosexual people. Epigenetics broadly concerns gene expression, although not entirely, through the manipulation of chromatin structure and function in both non-dividing and dividing cells. Epigenetic markings within the nucleus include the regulation of histones that effect how DNA is packaged and DNA methylation, which is the addition of methyl groups onto DNA nucleotides that affect gene expression. These regulatory mechanisms work together to help determine the three dimensional genome structure of DNA, which in turn effect gene expression. They do this by acting as the connection between environmental factors and internal factors within the peripheral tissues and brain, which then become molded and shaped based on these factors (Akbarian & Nestler, 2013). Epigenetics is the latest in recent studies on homosexuality which previously was controversial to research.
Until recently, homosexuality had been underrepresented within the animal population, this lack of reporting has been typically “associated with a historical reluctance to publish socially and religiously controversial information” (Rice, Friberg & Gavrilets, 2013). This practice has been reversed as more evidence has surfaced of the commonality and relative consistency of homosexuality amongst animals, including sheep at “about 8% strictly homosexual males” (Rice, Friberg & Gavrilets, 2013). This consistency is also translated over to humans. In the United States the percentage of the population who identify as lesbian, gay, bisexual, or transgender also known by the abbreviation, LGBT, was 3.5% as of February 2013 (Gallup, 2013). So what is the cause of homosexuality in the human population?
It has been found through research that there are physical differences in brain structure between heterosexual and homosexual people; these physical differences appear to be affected by hormones during prenatal development. There is evidence, from genetic testing that homosexuality is heritable; epigenetics has been found to significantly affect the way embryos interact with androgens through androgen signaling and the expression of genes that are involved in masculine behavior and phenotype, finally, through all this a new epigenetic model is starting to be used that could better explain what still needs to be done in order to find out the role of epigenetics in homosexuality.
3) Structural Differences
Differences between structure and the interaction of the brain and environment have been found to exist between heterosexual and homosexual men. One of the first differences in brain structure discovered between homosexuals and heterosexuals was that of the suprachiasmatic nucleus (SCN), which is used to “generate and coordinate hormonal, physiological, and behavioral circadian rhythms” (Swaab & Hofman, 1990). Swaab and Hofman (1990) also state that the SCN has also been linked to reproduction. Swaab and Hofman (1990) found that the SCN in “homosexual males were 1.73 times larger, and contained 2.09 times as many cells” than the heterosexual male reference group (Swaab & Hofman, 1990). Not only were there structural differences, other differences were found in how the brains of homosexuals react to the environment.
One difference that has been found is the way homosexual men and women’s anterior hypothalamus is activated compared to heterosexuals. It has been found that the anterior hypothalamus of heterosexuals has a certain sex-differentiated activation; this activation is almost reversed in homosexuals, making it sex atypical (Swaab, 2008). It has been found that in many areas of the brain homosexuals demonstrate a sex atypical reaction to many stimuli that cause a sexual differentiated response in heterosexuals. Deeper studies into the reasons why this happens have found that it is due to hormonal events that occur during fetal and prenatal development.
4) Hormonal Effects
When a fetus is developing in the uterus, fetal gonads develop between 6 and 12 weeks in boys because of the sex-determining gene on the Y-Chromosome. Females develop mainly because of the absence of androgens during development. After the development of the gonads, sexual differentiation then occurs in the developing brain (Bao & Swaab, 2011). There are two time periods between gonad development, the first two months of development, and brain development in the last half of pregnancy, the separateness of these two developmental time periods can cause independent development between the two that can lead to the rare possibility for genitalia and brain structure to not develop coherently.
One of the causes of sex difference in gender roles, gender identity, and sexual orientation is sex hormones in the developing brain. The main mechanism for this sex differentiation in the developing brain responsible for sexual identity and orientation is testosterone (Garcia-Falgueras & Swaab , 2010). Research has found that the fetal brain develops in a female direction if there is a lack of activity in regards to testosterone, and the fetal brain develops in a male direction if there is a direct effect involving testosterone on the developing brain (Garcia-Falgueras & Swaab , 2010).
There are specific examples of phenomena that have been found to be linked to the probability of a person being homosexual. In male children there are two significant periods of development where testosterone is higher than in girls. These developmental periods are mid-pregnancy and the first three months after birth. These peaks in testosterone are believed to affect the programming of a boy’s brain for his entire lifetime (Bao & Swaab, 2011). Changes and differences in these peaks could lead to a sexual differentiation of the brain that is atypical with the genital development of the child. Other examples of effects on the fetus while in the womb include the “fraternal birth order effect” which explains why, in boys, the possibility that a boy will be homosexual increases based on the number of brothers that were born before him. The theory of why this happens is thought to be “the progressive immunizations of some mothers to Y-linked minor histocompatibility antigens by each successive male fetus” (Bao & Swaab, 2011). This means that the mother starts to reject the male fetus as a foreign body and develops antigens to fight against it. These antigens can cause changes on how the fetus develops, creating a greater chance for the child to develop a homosexual orientation. Studies have also shown that exposure to thyroid gland hormone, nicotine, or amphetamines increases the chances of a mother to have a lesbian daughter (Bao & Swaab, 2011). It seems that there are postulated to be many different effects and factors surrounding sexual orientation development.
Evidence has been shown that hormones are insufficient to determine the actual cause of sexual orientation. This has been shown in studies that manipulate the gender and sex chromosome karyotype through the translocating of a gene that is responsible for male sex determination. This research has found that aspects of brain anatomy and sexually dimorphic behavior are strongly influenced by karyotype along with fetal androgen exposure (Rice, Friberg & Gabrilets, 2012). However, with this evidence it is still affirmed that androgen signaling is still the predominant factor. The reason that this is not the complete determinant is as follows. Through various studies on rats and humans it has been found that fetal androgen levels between both XX and XY fetuses overlap across all developmental stages. It has even been found that some XX fetuses have higher testosterone levels than other XY fetuses (Rice, Friberg & Gabrilets, 2012). These findings show that although androgens may play an important role, but they do not play a complete role.
Epigenetic marks that are dimorphic between XY and XX embryos are known to be produced during the genome-wide reprogramming of the embryonic stem cell stage. This stage is during the early development. The production of epigenetic marks have been found to greatly influence gene expression in later stages of development as well as have the ability to carry over across generations. These proliferations of epigenetic marks in the early stages are all but erased in the later stages of development except for a few, which include imprinted genes and active transposons (Rice, Friberg & Gabrilets, 2012). After this erasure there is once again another sequence of epi-marking known as “de novo epi-marking.” These are gene promoters that have been changed through DNA methylation and histone modification (Rice, Friberg & Gabrilets, 2012). This proliferation of epigenetic markings, erasure, and more epigenetic markings can have a profound effect on androgen signaling in both XY and XX fetuses during early development and later during perinatal development.
During the earliest stages of mammalian development there is clear evidence of epigenetic differences between XX and XY embryos. This includes differences in gene expression in hundreds of genes and how the embryos react to the environment. Also, prior to secretion of androgens by the testes, studies have shown that up to 51 genes in the brains of XY and XX embryos have differential expressions on their autosomes (Rice, Friberg & Gabrilets, 2012). Using this evidence, scientists have theorized that homosexuality could be caused by the heritable proliferation of epigenetic marks in the stem cell and not covered over by a de novo epigenetic mark later in development. This can explain the heredity of homosexuality, or if it was a de novo epigenetic mark it can explain why identical twins tend to have low concordance of sexual orientation (Rice, Friberg & Gabrilets, 2012). This topic will be discussed more in the next section. Even though hormones and epigenetic marks play a very important role in determining sex, gender, and sexual orientation, genetics has the capability of generating more information on the causation of homosexuality.
5) Genetics and Pedigree
Another important area of research into the causation of homosexuality within the human population is genetics. There have been a large amount of studies done in regards to this subject. Family and twin studies have found a possible genetic role in homosexuality. One such study examined the linkage between the X chromosome and homosexuality. The study performed by Hamer, Hu, et al.(1993), investigated genetic determinants in male sexual orientation, by using linkage analyses and pedigree on 114 families of homosexual men. One of the main results of this study was the discovery of a linkage between “homosexual orientation and markers in the distal portion of Xq28” (Hamer, Hu et al., 1993). This indicated the presence of a genetic predisposition to homosexuality coming from the inherited X chromosome. It however is important to note that due to the complexity of gender identity and sexual orientation more than one gene is probably affecting the occurrence of homosexuality. Other evidence of genetic factors involved in homosexuality was found in the first genome-wide scan of male homosexuals. In this study, three regions of genetic interest were found. The strongest of these genes was a gene located on “7q36” (Mustanski, Dupree, Nievergelt et al., 2004). There is found around this specific gene area a coding for a vasoactive intestinal peptide. This peptide has been found to be linked to the development of the hypothalamic suprachiasmatic nucleus in mice. As mentioned above this part of the brain has been found to be larger in homosexual men (Mustanski, Dupree, Nievergelt et al., 2004). This then shows a promising area to continue to study in order to find out more about how genetics affects homosexuality and whether an epigenetic activation of this certain gene increases the chance of a homosexual phenotype.
Studies using twin pairs to research empirical evidence of the heritability of homosexuality have been performed as well as gene analysis. These studies have sought to find whether there is a genetic or environmental connection on the causation of homosexuality. In the study done by Kendler, Thornton et al.(2000), they used a nationally represented sample of twins in the United States and found information on the sexual orientation of both members of the twin pair. In this sample, it was found that homosexual sexual orientation in identical twins was 31.6%. In another twin sample study, done in Australia by Bailey, Dunne and Martin (2000), consistent data was found that supports familial factors influencing sexual orientation, continuous gender identity, and childhood gender non-conformity. These different factors have been found to be genetically based with the finding that homosexuality tends to run in families. This study also found that homosexual orientation in identical twins was 20% for men and 24% for women. The study only found moderate to large heritability in regards to both female and male sexual orientation. This leads to the idea that there are still more factors involved than just genetics in the determination of sexual orientation (Bailey, Dunne & Martin, 2000). This has lead to current studies being done to determine the role of epigenetics in homosexuality.
6) Epigenetic Model
There are many reasons why scientists now believe that an epigenetic model for homosexuality can lead to a more overarching answer in regards to its prevalence in nature. One reason is how inconclusive many studies have shown to be when studying homosexuality. Studies have been able to find links to homosexuality in brain structure, prenatal hormone levels, and genetic markers, and have found heritability of homosexuality amongst families. These studies have sought to make sense of a phenomenon that occurs throughout nature. It has been found that homosexuality has been recorded to occur in 93 species of birds and many more animals (Rice, Friberg & Gavrilets, 2013). If a specific gene caused homosexuality, it would make sense that through natural selection the gene would be removed because only heterosexual intercourse can lead to procreation, so the gene could not be passed down. This reality requires another model in order to explain this, and the epigenetic model seems to be the best candidate to do so.
One idea that is currently being studied is prenatal stress in dysmasculinization of male mice in phenotypical expression involving behavior and physiological stress measures. The researchers examined the F2 generation (two generations down from original ancestor) that are descended from these prenatally stressed male mice to see if this epigenetic phenotype could be transmitted across generations. Using specialized equipment that study genes during neurodevelopment, they discovered a change in the mice’s gene expression to a female-typical pattern from a male-typical pattern in the F2 offspring of males that were prenatally stressed (Morgan & Bale, 2011). Changes were not only found at the level of observable behavior but also at the cellular and molecular level. As stated above, testosterone is essential in the masculinization and feminization of the brain. The researchers studied if a change was found in this process that could explain the male rats changed phenotype. It was found that the estrogen receptors “ERα and ERβ appeared upregulated, an effect suggestive of reduced ligand availability supporting a hypothesis for decreased perinatal testosterone in F2-S males” (Morgan & Bale, 2011).
The researchers continued to look for other differences and found that three miRNA’s (that help to regulate gene families in early neurodevelopment) expression seemed to be dysmasculinized including two that were significantly affected by the parental paternal prenatal stress. All three of the effected miRNA had β-glycan as a target. β-glycan is involved in regulating gonadal hormones like testosterone within the Leydig cells and pituitary gonadotrophs which can affect the dysmasculinization of the brain during development leading to sexually atypical behavior (Morgan & Bale, 2011). The study also looked at how miRNA expression affected sexual differentiation in the perinatal brain.
This was found through the use of an aromatase inhibitor, which prevented the testosterone from being converted to estradiol, which dysmasculinized the environment around the miRNA. After these males underwent testing, it was found that the male miRNA;s were not distinguishable from the control females. This data indicates a strong ability of organizational hormones on the expression of brain miRNA during the perinatal period. Along with the evidence of the effect of epigenetic mechanisms on gonadal hormones that influence sexual differentiation during development. (Morgan & Bale, 2011). This study helps strengthen the epigenetic argument of homosexuality because of the effect that was found from stress in previous generations and gene expression in subsequent generations in regards to dysmasculinization of behaviors. Despite these advances, there is still future research that needs to be done.
7) Future Research
In their paper titled “Homosexuality via Canalized Sexual Development: A Testing Protocol for a New Epigenetic Model,” Rice, Friberg, and Gavrilets (2013) explain several observations that they have made while combing through studies on homosexuality, that can be explained better through an epigenetic model rather than a genetic model. First, these observations conclude that homosexuality has a substantial heritability; however it has a low concordance when studied with both sexes of identical twins. Also, genetic markers are found in high density, but they don’t significantly associate with homosexuality. Second, homosexuality has too high of an occurrence among animal populations to be caused by a mutation, and homosexuality is not affected by natural selection. Third, genetic mutations involving androgen levels don’t seem to affect the sexual orientation of these individuals. The authors of this article then discuss how these different problems can be tested to find epigenetic underpinnings.
The first hypothesis that the authors suggest involves the inheritance of homosexuality and how it can be tested via an epigenetic model. The authors Rice, Friberg, and Gavrilets (2013) predict that an epigenetic model can be tested by studying and comparing the epigenetic profiles of “human embryonic stem cells” between heterosexual females and males and their homosexual counterparts. They predict that there will be a possibility of consistent differences in these epigenetic profiles in regards to sexual dimorphic epigenetic marks, which then would make the best candidates for finding those marks that cause the homosexual phenotype. The authors then say if this does not work, it can be narrowed down to focus around epigenetic androgen signaling. This model could help determine where these epigenetic marks are, or could lead to finding greater correlations between various systems that could help with the understanding of homosexuality.
The second hypothesis speaks on how homosexuality does not fit with natural selection and is too high and consistent to justify a mutation and therefore may be explained through an epigenetic model. The authors suggest that the best way to study this would be to use adult stem cells from homosexuals and heterosexuals and compare them to determine the difference in epigenetic marks that could help explain how they developed prenatally. This would have to be done with deceased individuals that have been preserved and prepared properly. An alternative to this would be to use hair follicle stem cells which can be differentiated into stem cells of the three embryonic layers. The stem cells will then have to be tested to see if they indeed do contain the needed information of epigenetic markings. If these stem cells make good candidates, then the stem cells of homosexual and heterosexual people of the same sex can be compared. The difference that the research can search for is the presence of “gonad-discordant epigenetic marks.” The authors say that failure to find these marks would prove this specific hypothesis wrong, because it would mean that no differences were found between homosexual and heterosexual people in regards to these specific epigenetic markings (Rice, Friberg, & Gavrilets, 2013). If these marks were found the third hypothesis could then be studied using the same technique as above. In order to determine the reason why mutations do not affect sexual orientation of the individual in regards to androgen signaling.
Scientists have continued to seek out the cause of homosexuality within the human and animal population and have found great success. The research however does not completely explain how all of the systems and chemicals in the body work together to create this phenotype. Much is already known about homosexuality, but new research that is focused around the role of epigenetics in homosexuality is beginning to help explain this phenomenon in greater detail. Scientists discovered physical differences in the structure of the brain between homosexuals and heterosexuals. More studies are linking hormonal effects, which are considered one of the single most important determinants of homosexuality, with epigenetic controls on hormone signaling. Genetics has also been found to play a role through the study of genome sequencing, multiple twin studies, and familial pedigrees. Significantly, scientists have discovered the effect of dysmasculinization on mice via various different epigenetic triggers that are created by stressful events during the development of the male parent. Even with all of this research, there is still room for future studies that can help explain the complex intersection between gender, sexual orientation, behavior, and physical characteristics.
Akbarian, S., & Nestler, E. J. (2013). Epigenetic mechanisms in psychiatry.Neuropsychopharmacology Review, 38(6), 1-2. doi: 10.1038/npp.2012.185
Bailey, M. J., Dunne, M. P., & Martin, N. G. (2000). Genetic and environmental influences on sexual orientation and its correlates in an australian twin sample. Journal of Personality and Social Psychology, 78(3), 524-536. doi: 10.1037/0022-35184.108.40.2064
Bao, A., & Swaab, D. F. (2011). Sexual differentiation of the human brain: Relation to gender identity, sexual orientation and neuropsychiatric disorders.Frontiers in Neuroendocrinolgy, 32, 214-226. doi: 10.1016/j.yfrne.2011.02.007
Gallup, I. (2013, Feb. 15). Lgbt percentage highest in d.c., lowest in north dakota. Retrieved from http://www.gallup.com/poll/160517/lgbt-percentage-highest-lowest-north-dakota.aspx
Garcia-Falgueras, A., & Swaab , D. F. (2010). Sexual hormones and the brain: An essential alliance for sexual identity and sexual orientation. Pediatric Neuroendocrinology , 17, 22-35. doi: 10.1159/000262525
Hamer, D. H., Hu, S. et al., (1993). A linkage between dna markers on the x chromosome and male sexual orientation. Science, 261(5119), 321-327. doi: 10.1126/science.8332896
Kendler, K. S., Thornton, L. M. et al., (2000). Sexual orientation in a u.s. national sample of twin and nontwin sibling pairs. American Journal of Psychiatry, 157(11), 1843-1846. doi: 10.1176/appi.ajp.157.11.1843
Morgan, C. P., & Bale, T. L. (2011). Early prenatal stress epigenetically programs dysmasculinization in second generation offspring via paternal lineage. The Journal of Neuroscience, 31(33), 11748-11755. doi: 10.1523/JNEUROSCI.1887-11.2011
Mustanski, B. S., Dupree, M., Nievergelt, C. M., & et. al., . (2004). A genomewide scan of male sexual orientation. Human Genetics, 116, 272-278. doi: 10.1007/s00439-004-1241-4
Rice, W. R., Friberg, U., & Gavrilets, S. (2012). Homosexuality as a consequence of epigenetically canalized sexual developement. The Quarterly Review of Biology, 87(4), 343-368. doi: 10.1086/668167
Rice, W. R., Friberg, U., & Gavrilets, S. (2013). Homosexuality via canalized sexual developement: A testing protocol for a new epigenetic model.Bioessays, 35, 764-770. doi: 10.1002/bies.201300033
Swaab, D. F., & Hofman, M. A. (1990). An enlarged suprachiasmatic nucleus in homosexual men. Brain Research, 537, 141-148. Retrieved from http://depot.knaw.nl/668/1/14928_285_swaab.pdf
Swaab, D. F. (2008). Sexual orientation and its basis in brain structure and function. Proceedings of The National Academy of Science, 105(30), 10273-10274. doi: 10.1073/pnas.0805542105