Immunological aspects of pregnancy in mules

Abstract

SummaryThe pregnant mare makes a range of immune responses to paternally‐inherited foetal histocompatibility antigens. Cytotoxic antibody is first detected in major histocompatibility complex (MHC)‐incompatible pregnancies by Days 50 to 70 of gestation. This follows shortly after the development of the endometrial cups and is concurrent with a striking accumulation of maternal lymphocytes and other mononuclear cells in the endometrial stroma around each cup. No such cellular infiltration occurs at the endometrium‐allantochorion border.The temporal coincidence between endometrial cup formation, cytotoxic alloantibody production and the accumulation of maternal lymphocytes suggests that these three events are interrelated. The relationships have been explored using immunogenetic markers in intraspecies horse pregnancy, by comparing immunological and endocrinological aspects of pregnancy in mares and jenny donkeys carrying normal intra‐specific and interspecific hybrid conceptuses and, finally, by examining foetomaternal interactions in sterile interspecies mules carrying pregnancies of both parental types created by embryo transfer. The working hypothesis has been that the endometrial cups are the source of immunogenic foetal histocompatibility antigen in equine pregnancy and that the cytotoxic antibody response and the lymphocyte accumulation around the cups represent humoral and cell‐mediated arms of the maternal immune response.Establishment of MHC‐compatible pregnancies demonstrated no significant effect of MHC differences between mother and foetus on serum equine chorionic gonadotrophin (eCG) levels, the duration of eCG secretion or the magnitude of the maternal leucocyte accumulation around the cups. Comparison of intraspecies horse and donkey pregnancies showed major differences between the two, including lower serum eCG levels, smaller endometrial cups with reduced leucocyte accumulation and a lower incidence of maternal sensitisation to foetal histocompatibility antigens in donkey pregnancy. Examination of interspecies mule and hinny pregnancies, on the other hand, showed a marked increase in the maternal lymphocyte reaction around the endometrial cups and a definite influence of the paternal genome of the foetus on eCG production.The successful transfer of horse and donkey embryos to female mules demonstrated that: (a) Both horse and donkey conceptuses express histocompatibility antigen in immunogenic form early in pregnancy; (b) both horse and donkey chorionic girdle cells can invade the endometrium of the mule to form endometrial cups, the eCG production rate of which is dependant upon foetal genotype; and (c) the magnitude of the lymphocyte accumulation around the endometrial cups does not correlate with known genetic differences between mother and foetus.