80 Several aspects

of equine pregnancy make its study useful in understanding eutherian materno–fetal interactions. In addition to the aforementioned maternal immune responses that distinguish the horse, its specialized trophoblast populations, combined with advances in assisted reproductive technologies, immunological reagents, and genomic resources, make the horse a uniquely valuable species in the advancement of pregnancy immunology. The trophoblast populations of human and horse placentas share significant phenotypic similarities. For each of the three principal types of equine trophoblast, there is a human counterpart (Fig. 4). The basic cell types and essential properties are conserved between these parallel groups, however BAY 80-6946 cost some functions have been distributed differently. The equine allantochorion trophoblasts correspond

to the human villous cytotrophoblasts (Fig. 4, orange). Both are mononuclear cells BAY 73-4506 chemical structure with stem cell-like properties that enable them to differentiate into other trophoblast types. They both express low levels of MHC class I mRNA, but not protein.32,81 The allantochorion trophoblasts are the primary mediators of nutrient exchange in the horse, whereas the syncytiotrophoblast layer provides this function in the human placenta. The chorionic girdle trophoblasts are similar to human extravillous trophoblasts (Fig. 4, red). Both cell types are invasive and migrate into the endometrial stroma. They both express MHC class I antigens from more than one locus, although the genes are not homologous.33,81–83 Lastly, the equine endometrial cup trophoblasts correspond to the human syncytiotrophoblasts

(Fig. 4, blue). Both cells types are multi-nucleate, sessile, and terminally differentiated. They suppress MHC class I gene expression at the transcriptional level38,81 and secrete chorionic gonadotropins. Only primate and equid species are known to produce placental gonadotropins.84,85 Additionally, recent molecular studies have identified transcription factors involved in trophoblast differentiation that are conserved between horse and human placentas.86 Another relevant similarity between human and horse pregnancy is the extended gestation length. The mare’s 340-day gestation allows adequate time for full engagement Fluorouracil nmr and commitment of the adaptive immune system. The resulting anti-paternal humoral immune response observed in nearly all mares carrying histoincompatible pregnancies is easily monitored through measurement of serum antibody levels.40,41 Up to day 36, the equine conceptus can be recovered non-surgically from the mare’s uterus, enabling the collection of pure trophoblasts that can be further investigated in vitro.87 The purified trophoblasts can be maintained in culture and driven to differentiate, allowing the opportunity for in vitro manipulation of specific populations.