Parental MHC antigen sharing and pregnancy wastage in captive pigtailed macaques

Among some human populations, immunogenetic similarity between mates is associated with increased risk of pregnancy loss. To investigate the relationship between histocompatibility and reproductive performance in non-human primates, 128 pigtailed macaque couples were classified as 'reproductively successful' or 'unsuccessful' according to previous breeding performance. These couples were arranged into 64 triads composed of individual females, and a 'successful' and 'unsuccessful' mate. Individuals were typed for class I MHC antigens using a microcytotoxicity technique and species-specific alloantisera. Matched-pair analysis revealed that significantly more 'unsuccessful' couples shared MnLA-A antigens than did the matched 'successful' couples. Conditional matched-pair logistic regression analysis further revealed that parental sharing of MnLA-A antigens is an even more significant predictor of pregnancy wastage than is advanced maternal age. In our study population, sharing of MnLA-A antigens predicted 72% of pregnancy loss among 'unsuccessful' couples (P < 0.009). Identification of histocompatibility-associated factors influencing pregnancy success could have profound clinical implications for chronic spontaneous abortion, intra-uterine growth retardation and birth defects in humans. Among captive primates, identification of MHC or MHC-linked genes affecting reproductive outcome could lead to more efficient colony management strategies as well as development of a model for understanding human immunologically-mediated reproductive failure.