Interspecific and extraspecific pregnancies in equids: anything goes

Equids possess the unusual ability to interbreed freely among the phenotypically and karyotypically diverse member species of the genus to produce viable, but usually infertile, offspring. The mule (female horse x male donkey) was humanity's first successful attempt at genetic engineering and its clear expression of both parental phenotypes has contributed much to our understanding of genetic inheritance over the centuries. Even more surprising, mares and donkeys have been shown to be capable of carrying to term a range of true, xenogeneic extraspecies pregnancies created by embryo transfer, including Przewalski's horse (Equus prezwalskii; 2n = 66)-in-horse, (E. caballus; 2n = 64), and Grant's zebra (E. burchelli; 2n = 44)-in-horse pregnancies. Fetal genotypes has a marked influence on placental development in equids, especially on the width and general development of the annulate chorionic girdle, progenitor tissue of the gonadotrophin (eCG)-secreting endometrial cups. However, transfer of intact and bisected demi-mule embryos (E. mulus; 2n = 63) to Jenny donkeys (E. asinus; 2n = 62) showed convincingly that maternal uterine environment, probably mediated by intrauterine growth factor production, can exert an overriding influence on chorionic girdle development and its invasion of the maternal endometrium. Transfer of donkey embryos (2n = 62) to horse mares (2n = 64) results in the development of an exceptionally small chorionic girdle that completely fails to invade the endometrium to form endometrial cups. Around 70% of these donkey-in-horse pregnancies are aborted between days 80 and 85 of gestation in conjunction with delayed and abnormal placental attachment combined with a vigorous maternal cell-mediated reaction against the xenogeneic donkey trophoblast. This model of pregnancy loss shows strong evidence of immune memory and the rate of fetal death is reduced by immunization of the surrogate mare against donkey lymphocytes. The findings suggest an important role for the invasive trophoblast cells of the equine placenta in initiating and driving attachment and interdigitation of the non-invasive placenta for fetal sustenance, and in modulating materno-fetal immunological interaction to enable survival of the antigenetically foreign fetus in the uterus.