A critical review of the role of the major histocompatibility complex in fertilization, preimplantation development and feto-maternal interactions

From conception to old age, the major histocompatibility complex (MHC) is a t the centre of immune responses that aid survival, fitness and adaptation of mammalian species to the environment. Its main function is that of contr olling adaptive immunity, particularly T-cell-mediated immunity towards pat hogens, In several species, including humans, the MHC is also able to elici t T-cell-mediated immune responses to allogeneic MHC antigens (non-self MHC antigens expressed by another individual from the same species). Although this phenomenon was originally identified in mice by the somewhat unnatural means of tissue transplantation, it was soon realized that it may also pla y an important role in the natural state, since the mammalian fetus in the maternal uterus is semi-allogeneic, due to the presence of MHC genes inheri ted from the father, Thus, during normal pregnancy the maternal immune syst em undergoes changes that lead to tolerance of the fetus. The MHC can play a dual role in the reproduction process: firstly influencing mating choice in some species, affecting the mother-father MHC matching; and secondly inf luencing the development of the fertilized ovum during the preimplantation period. In this review we examine the role of the MHC at three distinct lev els: (i) MHC expression in gametes and its role in fertilization; (ii) MHC expression in placental tissue; and (iii) MHC expression in embryonic tissu e. We suggest that the MHC plays a pleiotropic role, both in fitness (survi val and reproductive success) and in development, thereby ensuring the surv ival of the species in future generations.