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 homosexuality by approximately 33%. It has been hypothesized that this fraternal birth order effect reflects the progressive immunization of some mothers to Y-linked minor histocompatibility antigens (H-Y antigens) by each succeeding male fetus and the concomitantly increasing effects of such maternal immunization on the future sexual orientation of each succeeding male fetus. According to this hypothesis, anti-H-Y antibodies produced by the mother pass through the placental barrier to the fetus and affect aspects of sexual differentiation in the fetal brain. This explanation is consistent with a variety of evidence, including the apparent irrelevance of older sisters to the sexual orientation of later born males, the probable involvement of H-Y antigen 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 explain the recent finding that heterosexual males with older brothers weigh less at birth than heterosexual males with older sisters and homosexual males with older brothers weigh even less than heterosexual males with older brothers. Copyright 2001 Academic Press.