Placental Development

Uterine development, and subsequently endometrial-embryo interactions, are of paramount importance for animal production. Uterine gland differentiation and development occurs after birth in all studied mammals. Exposure of neonatal ewes to a progestin from birth to 8 weeks of age inhibits uterine gland differentiation, thereby creating an adult UGKO phenotype that exhibits recurrent early pregnancy loss. A series of publications using the UGKO ewe model established the unequivocal biological role of uterine glands and, by inference, their secretions in uterine receptivity and blastocyst survival, implantation, and placenta development. We have recapitulated those studies using mouse models. However, we have an incomplete understanding of:

  1. How glands interact with the developing embryo.

  2. How glands differentiate during the establishment of pregnancy.

  3. How can we model endometrial-embryo interactions in vivo.

Another active research focuses on understanding placental development in production animals. Cattle have a synepitheliochorial placenta characterized as semi-invasive, with maternal caruncles and fetal cotyledons forming highly vascularized placentome structures to facilitate nutrient exchange and fetal development. The synepitheliochorial placenta contains several trophoblast populations including binucleate cells, derived from the fetal trophectromerm and feto-maternal syncytium formed by binucleate cell fusion with the maternal uterine epithelial cells. However, the cellular complexity of the bovine placenta and the underlying mechanisms driving trophoblast differentiation and function are not well defined in vivo.

To this end, we are implementing single-cell RNA-sequencing and computational approaches to better understand the transcriptional landscapes of the developing placenta. In particular, we are focused on identifying transcription factors driving the differentiation of binucleate cells.