H-Y antigen is a male tissue specific antigen. Originally thought to trigger the formation of testes, it is now known that it doesn't trigger the formation of testes but may be activated by the formation of testes. In its production, there are at least two loci involved, an autosomal gene that generates the antigen and one that generates the receptor.
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The H-Y antigen secreted by the testis is identical to müllerian-inhibiting substance.
Association with spermatogenesis
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. 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.
Male homosexuality and the birth order effect
Among humans, it has been observed that men with more older brothers tend to have a higher chance of being homosexual - in fact, for every additional older brother, a man's chance of being homosexual can rise by up to 33%. 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 and thus the greater the inhibitory effect on brain masculinization, which is believed to be a factor in sexual orientation. 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'.