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
1)
Abstract
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.
2)
Introduction
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.
8)
Conclusion
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.
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