H-Y antigen

It has been shown that male mice lacking in the H-Y antigen, hence lacking in the gene producing it, have also lost genetic information responsible for spermatogenesis.[4] This result also identified a gene on the mouse Y chromosome, distinct from the testis-determining gene, that was essential for spermatogenesis, thus raising the possibility that the very product of this "spermatogenesis gene" is the H-Y antigen.[4]

Among humans, it has been observed that men with more older brothers tend to have a higher chance of being homosexual (see Fraternal birth order and male sexual orientation). For every additional older brother, a man's chance of being homosexual can rise by up to 33%.[5] One theory to explain this involves H-Y antigens, which suggests that a maternal immune reaction to these antigens has, to an extent, an inhibitory effect on the masculinization of the brain, and therefore, the more male foetuses that the mother of a man has had, the greater the maternal immune response towards him[6] and thus the greater the inhibitory effect on brain masculinization, which is believed to be a factor in sexual orientation.[5]

This hypothesis is supported by evidence that older sisters have no discernible influence on the sexual orientation of later-born males, which would be expected since H-Y antigen is male tissue specific, 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'.[7] More specifically, recent research (Jan 2018) has found maternal antigens to the neuroligin NLGN4Y protein, a Y-chromosome protein important in male fetal brain development, to be involved in the fraternal birth order effect.[8]