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The more older brothers a boy has, the more likely he is to be gay when he grows up – an effect called the “fraternal birth order effect”. Now it seems that increasing levels of antibodies in a mother’s immune system could play a role.

at Brock University, Canada, and his team think that some women who are pregnant with boys develop antibodies that target a protein made by the Y chromosome. Our immune systems make antibodies to recognise foreign molecules, which have the potential to be from dangerous bacteria. But pregnant women sometimes also produce antibodies against fetal molecules – for example, if their fetus has a different blood group. Bogaert’s team wondered if maternal antibodies might play a role in shaping sexual orientation.

The team collected blood from 142 women, and screened it for antibodies to a particular brain protein that is only made in males. They thought this would be a good candidate, because it plays an important role in how neurons communicate with each other, and because it is produced on the surface of brain cells, making it relatively easy for antibodies to find and detect it.

They found that the mothers of gay sons with older brothers had the highest levels of antibodies against this protein, followed by the mothers of gay sons with no older brothers. Women who had straight sons had less of these antibodies, while women with no sons had the least.

The team suggests these antibodies build up in some women’s bodies with every male baby they have. At higher concentrations, it is possible that the effect of these antibodies on the protein they target leads to changes in brain development that can have an influence on sexual orientation.

“I wouldn’t say we’ve solved the fraternal birth order effect puzzle, but we are getting close to finding a mechanism,” says Bogaert.

Brain wiring

The protein targeted by the antibodies, called NLGN4Y, is thought to play a role in how brain cells connect to each other, says Bogaert. “So it could affect brain structures that moderate attraction,” he says. “The mother’s immune response may alter the typical function of these brain structures.”

“This is a very important study because it provides a plausible mechanism to explain the fraternal birth order effect, perhaps the most firmly established phenomenon related to human sexual orientation,” says at Michigan State University. “Given that the protein is known to be important in synapse formation, you can see how maternal antibodies might affect the wiring of the fetal brain, and that might explain why each subsequent son is more likely to grow up gay.”

However, the team’s study only looked at a very small number of people, so strong conclusions cannot be drawn yet.

“The significance of this preliminary observation, if it can be replicated, is that it identifies specific molecules in the brain that may be important for heterosexual as well as homosexual development,” says Dean Hamer, a pioneer of researching the biological determinants of sexual orientation. The finding “could pave the way to a detailed neurobiological and genetic understanding of this fascinating aspect of human development”, he says.

Journal reference: PNAS, DOI: 10.1073/pnas.1705895114

Read more: What do the new gay genes tell us about sexual orientation?