THE EQUINE ENDOMETRIAL CUP REACTION - A REVIEW

The function of eCG in equine pregnancy is far from clear but it has b ecome evident that eCG has little or no FSH activity in the horse and is therefore probably not responsible for the secondary ovulations. eC G does have luteotrophic activity and it could play a role in the resu rgence of the primary corpus luteum (1,7,44). Some evidence exists tha t the receptor population on the equine gonads is heterogenous in a wa y that makes it possible to distinguish eCG from eLH, resulting in dif ferent post-receptor effects (7). There is also evidence that eCG itse lf is heterogenous, both in glycosylation and in primary structure, no t only between different individual animals but also within one animal during different stages of gestation. The differences could simply re flect the difference between stored and secreted hormone, but on the o ther hand the release of different eCG forms could be under endocrine control, allowing the mare to produce forms appropriate to specific bi ological needs (74). Thus some forms of eCG could play a role in immun ological events taking place at the foeto-maternal interface. The role of cytotoxic antibodies in the equine pregnancy is not understood. Th e fact that they are not harmful to the pregnancy can be explained by the fact that their target, the paternal MHC molecules, are withdrawn from the endometrial cup tissue by the time the antibodies start appea ring in the circulation. This unique way of regulation of MHC expressi on is also poorly understood. The functional role of the regulation of the expression of MHC class I antigens may be to give an immunoregula tory signal to the mare to provide an appropriate environment for impl antation (12). The down regulation of this expression could possibly b e regulated through a (cytokine mediated) feedback mechanism. The accu mulation of leucocytes has a strong temporal relationship with the for mation of the endometrial cups. It seems unlikely that MHC class I ant igens are the principal stimulus responsible for this reaction since t he accumulation appears to be equal in histocompatible and histoincomp atible pregnancies, but future developments in ELA-antigen typing may prove this to be otherwise (19,27,87). A second candidate could be the trophoblast specific antigen that has been found on the equine tropho blast, but this is also unlikely because this antigen is expressed at both the invasive and the non-invasive part of the trophoblast and leu cocytes only accumulate near the endometrial cups (69). The possible r ole of eCG as leucotactic substance has not been evaluated. The other remaining possibility is the assumption that the influx of leucocytes is a response to the tissue damage done by the invading chorionic gird le cells, thus resembling an inflammation reaction. Similarities betwe en the uterine response to implantation and an immune inflammatory res ponse have frequently been noted by several authors (78,80). The fact that the foetus is not harmed by all the immunological activities taki ng place could arise from a combination of immunosuppressive and immun otrophic events combined with a trophoblast that is neutral to putativ ely harmful responses. The combination of these events is not a priori contradictory. The presence of a large array of different cells at th e foeto-maternal interface opens the possibilities for a complex regul atory network. This could also apply to equids since it has been repor ted that the endometrial cup leucocyte population comprises lymphocyte s, lymphoblasts, macrophages, large granular lymphocytes (78), eosinop hylic leucocytes, NK cells, and cells with suppressive properties in v itro (47,75). Neither total suppression nor total trophic reactions pr ovide satisfying explanations for the events taking place at the foeto -maternal interface. The discovery of a large array of cytokines and o ther soluble factors in murine and human pregnancy as well as specific receptors for these substances on immune cells and trophoblast cells seems to fit the concept of an extensive endocrino-immunological netwo rk which regulates pregnancy (20,80). In the donkey-in-horse pregnancy , the donkey conceptus fails to make the initial contact with the mate rnal immune system and this could be responsible for a serious failure in bidirectional cytokine communications, resulting in failure of the pregnancy. All in all, many questions about the endometrial cup react ion in equids are unanswered and await future research.