Fraternal birth order and the maternal immune hypothesis of male homosexuality

In men, sexual orientation correlates with an individual's number of older brothers, each additional older brother increasing the odds of homosexualit y by approximately 33%. It has been hypothesized that this fraternal birth order effect reflects the progressive immunization of some mothers to Y-lin ked minor histocompatibility antigens (H-Y antigens) by each succeeding mal e fetus and the concomitantly increasing effects of such maternal immunizat ion on the future sexual orientation of each succeeding male fetus. Accordi ng to this hypothesis, anti-H-Y antibodies produced by the mother pass thro ugh the placental barrier to the fetus and affect aspects of sexual differe ntiation in the fetal brain. This explanation is consistent with a variety of evidence, including the apparent irrelevance of older sisters to the sex ual orientation of later born males, the probable involvement of H-Y antige n in the development of sex-typical traits, and the detrimental effects of immunization of female mice to H-Y antigen on the reproductive performance of subsequent male offspring. The maternal immune hypothesis might also exp lain the recent finding that heterosexual males with older brothers weigh l ess at birth than heterosexual males with older sisters and homosexual male s with older brothers weigh even less than heterosexual males with older br others. (C) 2001 Academic Press.