Volume 95 Issue 49 | p. 6 | News of The Week
Issue Date: December 18, 2017 | Web Date: December 13, 2017

A mother’s immune system could influence sons’ sexual orientation

Antibodies produced from carrying multiple male fetuses could help explain why having older brothers increases a man’s likelihood of being gay
Department: Science & Technology
Keywords: Neuroscience, psychology, sexual orientation, immunology, Y chromosome
Mothers’ immune systems may target brain proteins encoded on the Y chromosome (shown) in male fetuses.
Credit: Biophoto Associates/Science Source
A micrograph of a Y chromosome.
Mothers’ immune systems may target brain proteins encoded on the Y chromosome (shown) in male fetuses.
Credit: Biophoto Associates/Science Source

The greater number of older brothers a man has, the more likely he will be homosexual. Researchers have observed this so-called fraternal birth order effect across societies and over time. Now scientists report a possible biological mechanism behind it.

They found that mothers of gay men with older brothers have elevated levels of antibodies against a male-specific brain protein (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1705895114). The findings support the hypothesis that a mother’s immune response could shape brain structures in male fetuses that are involved in the development of sexual orientation, the researchers say.

The fraternal birth order effect is one of the most robust correlations uncovered in sexual orientation research, and this study is an important first step in understanding the biology underlying the effect, says Qazi Rahman of King’s College London, who was not involved in the work.

Anthony F. Bogaert of Brock University and Ray Blanchard of the University of Toronto first observed the phenomenon in a Canadian population in 1996. Since then, researchers have replicated the findings in societies across the globe. The two psychologists even went back through data collected in the 1940s and 1950s by Alfred Kinsey of Indiana University, who conducted some of the first research on human sexuality, and observed that the effect existed then.

Despite its ubiquity, the effect is modest, Bogaert points out. About 2-3% of men without older brothers are gay. Having four or more older brothers increases that rate to about 6%. So the vast majority of men with multiple older brothers are heterosexual.

About 10 years ago, Bogaert reported data pointing to a biological origin for the phenomenon, instead of a social one. The findings showed that growing up with older step or adopted brothers doesn’t increase a man’s likelihood of being gay, but having older biological brothers who grew up elsewhere does. “It really suggested that there was a before-birth effect and that childhood or adolescence was not playing a role,” Bogaert says.

He and Blanchard had a hypothesis about the biology underpinning the phenomenon. They thought that mothers’ immune systems might treat a specific protein in male fetuses like a foreign invader and this response would grow stronger with each boy born to the same mother. Eventually, the immune response would influence the developing brain of a son born later among a line of male siblings.

To test the hypothesis, the psychologists teamed up with some immunologists and collected blood samples from 54 mothers of gay sons, 72 mothers of straight sons, 16 women with no sons, and 12 men. They were looking for antibodies that target male-specific proteins.

One of the ways our immune systems remember foreign proteins is through antibodies circulating in our blood, says Brock University’s Adam J. MacNeil, who was one of the team’s immunologists. Detecting these antibodies basically gives us a glimpse of what the immune system bumped into in the past, he adds.

The team was interested in two proteins encoded on the Y chromosome—protocadherin 11 Y-linked and neuroligin 4 Y-linked. Both proteins are expressed in the fetal male brain and both have parts that stick out of cells, making them possible targets of a mother’s immune system.

The researchers found that mothers of homosexual sons had higher levels of antibodies for the neuroligin protein than did mothers of heterosexual sons, and mothers of gay sons with older brothers had even higher levels. There was no trend for antibodies targeting the protocadherin protein.

Not a lot is known about the function of the neuroligin protein except that it helps form connections between brain cells and facilitates communication between them, MacNeil says.

Because the study’s sample size was small and the observed effect was modest, Rahman thinks the experiment should be replicated on a larger scale to confirm the results. Bogaert also hopes other groups will try to replicate it: “One study just won’t cut it,” he says.

Also Bogaert says it’s important not to think of this mechanism as a disorder—as something pathological caused by a mother’s immune response. “An atypical biological process creating a trait doesn’t mean that the trait it produces necessarily needs fixing,” he adds.

In general, he says, work on uncovering the biological basis for sexual orientation has helped the gay rights movement. “It suggests that sexual orientation is not a choice,” Bogaert says. “It also resonates with gay people’s lived experience—that they have felt different from early on in their lives.”

Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
William Brewer (Thu Dec 14 11:26:47 EST 2017)
The article is good except for its side-trip into LGBT ideology by failing to point out the fact-meaning fallacy of equating the existence of a biological mechanism with whether or not the results need "fixing."

While it is false that such a link implies homosexuality is a bad thing. It's also false that such a link implies homosexuality is a good thing as well. If you going to say one thing you need to say the other too.

All of the last paragraph is inappropriate to a scientific article unless you're going to use it to show the researcher's bias.

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J. Bell (Wed Dec 20 17:03:12 EST 2017)
C&EN is not a scientific journal. It is a scientific news magazine. As such, an article can appropriately include a superficial exploration of the possible societal implications of a discovery in chemical biology.

After millennia of proclamations by religious authorities regarding the sinful and evil choices that constituted the presumed 'cause' of homosexuality, shedding a small amount of light on that situation in C&EN is not at all objectionable. I would be glad to see a feature article describing all of the evidence that homosexuality is often not a matter of choice.
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Dan Chang (Wed Dec 20 14:37:31 EST 2017)
This story is based on a small sample discovery ,with big claim. Definitely this claim is not a scientifically sound conclusion. I am eager to seeing a real scientific conclusion. I also find that some scientists reported a statement by saying I believe..... or it is possible.... Believe is a faith, not a science. A possibility is a speculation, not a fact. Thanks.
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William Rubin (Tue Jan 02 00:38:19 EST 2018)
Well said! The research this article exemplifies is a joke - very small yet somehow draws big conclusions. Obviously, the results were interpreted by a liberal, scientific bias. This crap needs to stop in society. What else are we going to rationalize on the "basis of science"? When is American society going to stop with the PC BS and define what is repulsive and objectionable as such.
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P Southon (Wed Dec 20 21:41:02 EST 2017)
This research opens up a very controversial possibility: Imagine a biotech company offering a treatment for mothers-to-be which reduced the chances of their sons being gay. I foresee an opportunity for much profit, debate and soul-searching.
Stan J. (Thu Dec 21 22:02:06 EST 2017)
I think the impact of this discovery will be massive. What is the evolutionary explanation for this? What else can control neuroligin? What factors (other than having more older brothers) increases production of the antibody controlling neuroligin?
Glenn Stafford (Sat Dec 23 00:12:02 EST 2017)
It troubles me that such a preliminary study could be used to support a personal belief. It does not seem to me that the results of the study would warrant the statements of the last paragraph. The term homosexual typically describes a person's sexual behavior. It is does not follow that such individuals with high levels are compelled to engage in homosexual activity. Homosexual activity by such individual is still based on choice and learned behavior and cannot be considered natural on the same level as heterosexual sexual intercourse.
bradd graves (Thu Dec 28 08:01:26 EST 2017)
Gee, Glenn, reaching for "different levels of natural" are we? Seems you're the one stuck on a belief, not the authors.
William Rubin (Tue Jan 02 01:15:23 EST 2018)
Gee, bradd, it sounds like you're the pot calling the kettle black!
Angry (Sat Dec 23 12:47:01 EST 2017)
This is not science, but a liberal agenda trying to make natural what is logically unnatural. Being a sodomite is matter of choice not biology. Biology may serve as an occasion for the lifestyle, in much the same way that elevated levels of testosterone are the occasion for high sex drives or anger in men. In the end, we are not slaves of our biology but our wills; we choose what we want, even if it’s aberrant. Stop spouting off your liberal agenda in this scientific journal!
Janice LaBrie (Tue Dec 26 19:56:38 EST 2017)
There is evidence of homosexuality in some animals (deer for example) when the food supply is diminishing because of over-population. That could be viewed as logically natural. We are animals ourselves, with our biology controlling much of our behavior.
William Rubin (Tue Jan 02 00:42:55 EST 2018)
Wow, one example! Good science.
KM (Fri Dec 29 07:29:21 EST 2017)
Angry - please provide peer reviewed science literature citations that support your claim that homosexuality is a choice and not biology. This is, after all, a scientific journal.
William Rubin (Tue Jan 02 00:32:34 EST 2018)
KM - please provide unbiased peer-reviewed evidence that supports YOUR assumption that homosexuality is not a choice. Here is some evidence (and a lot more out there, you just have to be willing to conduct research in an objective manner), although I won't be surprised if you try to discredit it to fit your liberal narrative/agenda. This is an inconvenient truth to many liberals, but there is a high correlation (causalty? - probably) between being molested and choosing a gay lifestyle -

And, by the way, why does your evidence require a "scientific" supposition? There are many aspects of reality that cannot be understood through the finite human lens and understanding of empiricism. Stop being so close-minded.
KM (Tue Jan 02 19:53:32 EST 2018)
William Rubin - My comment to Angry simply points out, without name calling or insult, that he/she chastised the authors of the CEN article for not basing the article on science, but on "a liberal agenda". Angry did that by stating his/her opinion only, providing no science to back it up. Given that the CEN article is, in fact, based on a peer reviewed scientific publication, it is seemingly lost on Angry, and also on you, that Angry is actually the one guilty of what he/she accused CEN of.

Furthermore, there are many publications providing evidence of various causes of homosexual behavior. Is it due to choice in some cases? Probably. Is some due to genetics/biology in others? Probably. Is it due to only one or another, absolutely? Highly unlikely.
William rubin (Wed Jan 03 10:37:57 EST 2018)
KM - you still haven't provided any evidence to support your claim. There is also much evidence out there, as I have already stated, that actually the opposite is true - that sexual abuse is a significant cause of homosexual tendencies leading to a homosexual lifestyle. You just actually have to circumvent your extreme bias, which is quite evident. Science is based on evidence that is involves a significant number of pooling subjects. Given that "blood samples from 54 mothers of gay sons, 72 mothers of straight sons, 16 women with no sons, and 12 men", does not represent a statistically significant pool, the scientific credibility of the "research" is very questionable. Angry and I have it correct, you seem to be the one that is unable to understand that scientific reports can be disavowed due to the authors' high bias. Angry and I are not accusing C&ENews of anything. We are accusing the article they are reviewing as being unscientific and the impetus of the conclusion based on bias, not science. Apparently, you are unable to differentiate between the two, which unfortunately, many Americans are unable to do. Thus, when "science" is conducted and interpreted by bias, the conclusions are opinion, which is what you are accusing Angry of. My advice to you is, be careful what you define as opinion, because what you assume to be science-based just b/c an article appears in a peer-reviewed journal, may actually just be an opinion, not fact, and thus deceive yourself. (Just to set the record straight, I'm not name calling, I'm just pointing out that you seem to have a very myopic manner of dealing with this topic).
KM (Fri Dec 29 07:42:21 EST 2017)
Angry - furthermore, I would point out that approximately 1 in 1500 to 1 in 2000 human births are intersex, where the genitalia are obviously (visually) neither female nor male, but somewhere in between. This frequency is greater when less obvious forms of genital variation are considered. Given this clearly biological fact, it would be entirely logical to expect similar biological variation in sexual orientation/behavior.
William Rubin (Tue Jan 02 00:51:21 EST 2018)
Bullseye! Very good point that many people need to hear.
William Rubin (Tue Jan 02 01:14:39 EST 2018)
Angry is right on target. It's unfortunate that if he reveals his name, he would probably be ostracized by a very close-minded, judgmental, and intolerant scientific community.
Patrick Gallagher (Wed Jan 03 17:56:34 EST 2018)
Please explain what you mean by “logically unnatural”. I find your discussion and conclusions woefully lacking in logic. If you can’t make better arguments your causes will be furthered if you are silent.
Quinn Montana  (Thu Dec 28 12:25:00 EST 2017)
The article and all it's commentators seem to view "gay" and "straight" as a binomial states of being rather than as among a spectrum. What if, instead of viewing "gay" as a "thing" we saw it as an enhancement or exacerbation of the desire to get along, to work cooperatively?

We all know that testosterone creates combativeness and competition, especially in relation to other males. In a small community of ancient times, it would be imperative that males cooperated for the sake of the community.

What if this protein mitigator isn't an example of "foreign bodies doing battle" (such a typically male interpretation) but an adaptation within the mother's body to ensuring that her offspring would survive rather than kill each other?

Each consecutive male born may have an enhanced ability to want to work with and get along with other males, which eventually manifests as attraction to (especially in conjunction with various other possible influences both social and biological) other males.

Not only biologically normal, but necessary. And therefore perhaps the highly combative males are as much outliers as those at the other end of the spectrum, and "normal" is in the middle.

» Reply
William Rubin (Tue Jan 02 00:49:42 EST 2018)
Spoken like a person who interprets all of creation through an evolutionary set of specks. A ridiculous pontification. It's pathetic how evolutionists are always trying to interpret "data" to fit their hypothesis (actually, an immutable assumption or supposition), instead of the other way around. Try practicing exegesis instead of eisegesis.
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