Evidence for major histocompatibility complex-mediated effects on spermatogenesis in humans

Studies in fertile and infertile populations suggest an influence of genes of the major histocompatibility complex (MHC) on reproduction, although it remains unresolved if MHC-mediated effects on fertility are based on direct immunological or non-immunological effects of human leukocyte antigen (HLA) genes or rather on defects in MHC-associated non-HLA genes which affect gamete quality and embryonic development. We analysed allele frequencies for HLA class II loci DQA1, DQB1 and DRB1 and HLA class II haplotype frequencies in couples with tubal and andrological infertility who were treated with assisted reproductive techniques. Males with severe andrological infertility had significantly different allele frequencies for all three HLA loci when compared to males with normozoospermia, whereas no difference was found in the females. Differences in allele frequencies were stronger when only males whose partners achieved pregnancies after assisted reproduction treatment were compared. In those subgroups, we could also observe significant differences in three locus HLA class II haplotype frequencies. In summary, patients with male factor infertility differ in their HLA class II allele constitution from males with normozoospermia, which suggests that genes identical to or located in close vicinity to HLA class II genes may influence spermatogenesis and male gamete function.