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An Inquiry of the Maternal Immune Hypothesis
October 1, 2010
Homosexuality has been an observable human behavior since ancient times. More recently, however, homosexuality’s biological and psychological underpinnings are being questioned and tested in quantitative fashions. Researchers debate whether sexual orientation can be primarily attributed to genetic or environmental circumstances, or a combination of both. The fraternal birth order effect describes a strange phenomenon in which male sexual orientation correlates with a male’s amount of older brothers. In males, fraternal birth order is actually the best predictor of sexual orientation (Bogaret 2006). Two major observations underlie the fraternal birth order effect. The first is the observation that, typically, homosexual males have more older brothers than heterosexual males (Blanchard 2001). The second major observation is that each additional older male sibling increases the likelihood of homosexuality for a male individual by approximately 33% (Blanchard 2001). The fraternal birth order effect identifies the prenatal environment as a determinant for male sexual orientation. This paper is an inquiry of the maternal immune hypothesis. It intends to explain the maternal immune hypothesis and its relation to the fraternal birth order effect, while also explaining the fraternal birth order effect and its relation to male sexual orientation. More simply, it questions if, and to what extent, prenatal circumstances, particularly fraternal birth order, affect sexual orientation in males.
The Maternal Immune Hypothesis
The maternal immune hypothesis, put forward by Blanchard & Bogaret in 1996, explains the fraternal birth order effect as possibly resulting from the progressive immunization of mothers to male fetuses. This immunization would result in a maternal immune attack incited by a male fetal antigen, and would increase after every pregnancy with a male fetus. Blanchard & Bogaret suspected and hypothesized that this male fetal antigen was the H-Y antigen. This theory would help to explain the fraternal birth order effect. First, it clarifies why only older brothers, and not older sisters, increase the likelihood of a male child being homosexual. Second, it elucidates why the higher the birth order of a male, the greater his chances (as mentioned before, 33% increase after each additional older male sibling) of being homosexual; or, more simply, why typically male homosexuals have more older brothers than male heterosexuals. (Blanchard & Klassen 1996)
What is the H-Y Antigen?
In order to understand the fraternal birth order effect, some researchers look for an immunologic explanation. To understand the maternal immune hypothesis, it is important to first understand the supporting science behind it. The Maternal Immune Hypothesis proposes that a certain fetal antigen, found only in male fetuses, causes an immune response from a pregnant woman that increases in strength with each subsequent pregnancy. More specifically, researchers have supposed that this antigen may be what will be referred to as the H-Y antigen, a male-specific antigen. In humans, the H-Y antigen is most likely a component in sexually differentiation for two reasons. First, the H-Y antigen is present only in males, which is the heterogametic sex – the sex with two different sex chromosomes (in humans, the male has an X and Y chromosome) and not in females, the homogametic sex (women possess two X chromosomes). Additionally, the presence of the H-Y antigen has endured throughout the duration of vertebrate evolution, signifying its vitality to the perseverance of the human race. (Blanchard & Klassen 1996)
How does the H-Y antigen influence male sexual orientation?
It is because of the likelihood that the H-Y antigen is involved in sexual differentiation that it is suspected in affecting male sexual orientation. In a 1991 study by Simon Levay, the volumes of four cell groups in the interstitial nuclei of the hypothalamus (INAH) were measured and compared between postmortem heterosexual males, homosexual males, and heterosexual females. It was observed that INAH 3 was twice as large in heterosexual males as in heterosexual females. Additionally, INAH 3 was twice as large in heterosexual males than in homosexual males. First, this study greatly strengthens the notion that male sexual orientation has a biological root. Additionally, this study is compatible with the H-Y antigen theory and the maternal immune hypothesis, as it exhibits that sexual orientation may be the result of brain dimorphism of the sexes. It further strengthens the H-Y antigen theory because it is believed that H-Y antigens probably affect sexual orientation by in shaping the fetal brain in a way atypical from that of a heterosexual male. (Levay 1991).
How does this support the Maternal Immune Hypothesis?
The H-Y antigen, which differentiates between male and female fetuses, could logically be the marker that alerts a mother’s immune system and provokes an attack. Assuming that the H-Y antigen is in fact the antigen, because male fetuses carry the H-Y antigen, a woman’s immune system would only be able to create a “memory” of the amount of male fetuses she has carried (and not female). By having this “memory” of the number of previous males fetuses carried, a woman’s immune system could effectively respond to the presence of a male fetus, and would logically have a more dramatic response with each additional older male sibling. This evidence helps support how the H-Y antigen might fit the Maternal Immune Hypothesis because the necessary antigen to provoke a response needs to be sex-specific, like the H-Y antigen. (Blanchard & Klassen).
Speculation of The Maternal Immune Hypothesis
N.E. Whitehead in his examination of the maternal immune hypothesis, approaches with great speculation the theory that homosexuality can be attributed to the maternal immune hypothesis. He provides arguments that point to the contrary of the maternal immune hypothesis.
Anti-male Antibodies and Immune Response Prevalence
First, Whitehead brings into question the existence of anti-male antibodies. The Maternal Immune Hypothesis supposes that the mother’s body, in resistance to the H-Y antigen, develops H-Y antibodies, which then attack the male fetus. In known antigen attacks, mothers develop antibodies against paternal, and not specifically male, antigens. Whitehead further points out that the statistics do not match up. A 0.4% prevalence is estimated for homosexual males with older brothers. However, the most common alloimmune condition, NAIT, only has a prevalence of 0.1%. If the presence of an anti-male antibody existed at the same rate as the most common alloimmune condition, it would still be greatly under the estimated prevalence of homosexual males due to the maternal immune hypothesis. (Whitehead 2007).
Absence of Testis Attack
Whitehead also points out that the testis, which contain far more male-specific proteins should be the prime target for an immune attack. To the contrary, there is no detected testis immune attack in homosexual males. Thus, a supposed brain attack seems unlikely. Additionally, if the maternal immune hypothesis is true, and there is indeed an immune attack on the brain, it is unusual that there is no other known neurlogoical damage that is the result of the fraternal brother order effect. Whitehead cites a comprehensive study that tested if sons born of a higher order (later-born sons) exhibited a correlation with other neurological problems. No correlation was found, further undermining the maternal immune hypothesis. (Whitehead 2007).
Only Older Biological Brothers
The fraternal brother effect is based off the observation that the only sibling characteristic which predicts male sexual orientation is biological older brothers. Anthony F. Bogaret, 2006, did a comprehensive study to test the observed fraternal brother effect. Bogaret wanted to test if it was the social or biological presence of older brothers that caused the fraternal birth order effect. Bogaret studied four samples of homosexual and heterosexual men, one sample being reared in nonbiological or blended homes (adoptees or those reared with step- or half-siblings). For the first three groups, information was collected on biological and nonbiological siblings. From the fourth group, the men from nonbiological/blended homes, information was collected about how much time the individuals were raised with each sibling and information on biological siblings with whom they were not raised. Bogaret was able to conclude that it is highly likely that homosexuality stems from the prenatal environment due to the observation that the only sibling characteristic that served as a predictor for male sexual orientation was the amount of elder biological brothers. Furthermore, not only is older brothers the only sibling characteristic that serves as a predictor for male sexual orientation, but Bogaret notes that fraternal birth order has the most reliable correlation with homosexuality in males. (Bogaret 2006).
Ray Blanchard, a top researcher in the field of male homosexuality, provides a bevy of statistics and evidence supporting the fraternal birth order effect and the maternal immune hypothesis in a dissertation on male homosexuality. He provides an epidemiological identification of the population attributable risk. The population attributable risk is the “proportion of all gay men who acquired their sexual orientation via the older brother route” (Blanchard 2001). It is the sum of attributable fractions for gay men with n older brothers weighted by the proportions of gay men who have n older brothers (Blanchard 2001). Blanchard cites a study in which the attributable risks were calculated, and observed that approximately one out of seven homosexual males can attribute his sexual orientation the fraternal birth order effect. That is to say that if the mothers of these one in seven males had only carried females prior to the birth of their homosexual son, the sons should, in theory, have been born heterosexual (Puts et. Al, 2006). Blanchard also examines a study that identifies 2.5 brothers as the tipping point of attribution for younger brother homosexuality; more simply, for homosexual men with 2.5 older brothers, the cause of homosexuality is the fraternal brother effect. (Blanchard 2001).
Weighing all the evidence does not provide a clear answer if the maternal immune hypothesis is in fact a certain biological explanation of male sexual orientation. For example, as stated above, Blanchard observes that it is a fact that, on average homosexual males, when compared to heterosexual males have a higher number of previously born male siblings (Blanchard 1991). It is also true, however, that there exist more homosexual males than the fraternal birth order effect can account for (Whitehead 2007). It is unreasonable to expect the fraternal birth order effect, or any other one reason to completely and cleanly explain male sexual orientation, but it is very significant to note that as the most consistent predictor of male sexual orientation, it is doubtful that the fraternal birth order effect is merely a coincidence (Bogaret 2006). Therefore, it seems reasonable to conclude that there are multiple causes of male homosexuality, perhaps linked or unlinked, in which the H-Y antigen, maternal immune hypothesis, and the fraternal birth order effect may or may not be underlying factors.
Blanchard, Ray. “Fraternal Birth Order and the Maternal Immune Hypothesis of Male Homosexuality.” Hormones and Behavior 40.2 (2001): 105-114. Web. 5 Sept. 2010. <http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WGC-45B5PPP-5&_user=86629&_coverDate=09%2F30%2F2001&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000006878&_version=1&_urlVersion=0&_userid=86629&md5=cd0ddad489a52ccad020a34a477dc5bb&searchtype=a>.
Blanchard, Ray. Philip Klassen, H-Y Antigen and Homosexuality in Men, Journal of Theoretical Biology, Volume 185, Issue 3, 7 April 1997, Pages 373-378, ISSN 0022-5193, DOI: 10.1006/jtbi.1996.0315. <http://www.sciencedirect.com/science/article/B6WMD-45KKS7X-72/2/bb2ced0f0b7f543f6c62ccaad33ca187>
Bogaert, Anthony F. “Biological versus nonbiological older brothers and men’s sexual orientation.” Proceedings of the National Academy of Sciences of the United States of America 103.28 (2006): 10771-10774. Web. 5 Sept. 2010. <http://www.pnas.org/content/103/28/10771.full.pdf+html>.
Levay. Simon. “A Difference in Hypothalmic Structure Between Heterosexual and Homosexual Men” American Association for the Advancement of Science 253 (Aug. 1991): 1034-1037 JSTOR Science Web. Sept. 2010. <http://www.jstor.org/stable/2878803?seq=1&Search=yes&term=levay&term=simon&list=hide&searchUri=%2Faction%2FdoBasicSearch%3FQuery%3Dsimon%2Blevay%26wc%3Don%26acc%3Don&item=1&ttl=162&returnArticleService=showFullText&resultsServiceName=null>
Puts, David A., Cynthia L. Jordan, and S. Marc Breedlove. "O brother, where art
thou? The fraternal birth-order effect on male sexual orientation."
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America 103.28 (2006): 10531-10532. Web. 5 Sept. 2010.
Whitehead, N. E. “An Antiboy Antibody? Re-examination of the Maternal Immune Hypothesis.” J Biosoc Sci (Feb. 2007): 905-921. ProQuest Psychology Journals. Web. 5 Sept. 2010. <http://proquest.umi.com.proxy.library.vanderbilt.edu/pqdweb?index=18&did=1354055381&SrchMode=1&sid=2&Fmt=6&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1283741386&clientId=622>.
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