Ectopic Transplantation of Equine Invasive Trophoblast1

Abstract

A system for transplanting invasive equine trophoblast (i.e., chorionic girdle) to ectopic sites has been developed as a means to study the differentiation of this tissue and to assess maternal immune responses to the conceptus tissue in a site outside the uterus. Chorionic girdle was isolated from Day 33 to 34 conceptuses and surgically placed into the vulvar mucosa or subdermal skin of recipient mares. Biopsy specimens of the graft sites for immunohistochemical staining were taken at weekly or biweekly intervals after grafting. Serum samples were collected from each recipient and tested for antibody to donor major histocompatibility complex (MHC) class I antigens using the lymphocyte microcytotoxicity assay. Transplanted trophoblast cells expressed differentiation markers associated with invading chorionic girdle and endometrial cup cells. The transplanted trophoblast cells were also labeled by an antibody to eCG. Strong cellular and humoral immune responses to the transplanted tissue were mounted by the recipients, similar to those occurring during normal equine pregnancy. Despite these responses, the invasive trophoblast transplants survived for at least 28 days after grafting and downregulated MHC class I antigens, as do the mature endometrial cup cells in equine pregnancy. These findings suggest that invasive equine trophoblast has the capacity to differentiate fully in equine nonuterine tissues, and that it can evade maternal immune responses independent of the physiological state of pregnancy and in sites other than the uterus.

Functions of ectopically transplanted invasive horse trophoblast

“…A recent study of ectopic transplantation of trophoblast stem cells in mice demonstrated their capacity to survive for several months and to modulate their local immune environment (Epple-Farmer et al 2009). Previous studies from our group have shown that equine chorionic girdle binucleate trophoblast cells survive for at least 28 days after transplantation in ectopic sites such as the vulvar mucosa and under the skin (Adams & Antczak 2001, de Mestre et al 2008). At 28 days post-transplantation, the trophoblast cells were terminally differentiated and restricted to the transplant site, suggesting that they do not proliferate or migrate (Adams & Antczak 2001, de Mestre et al 2008).…”

Evolution of Placentation in Primates: Implications of Mammalian Phylogeny

“…Those cells migrate through the uterine epithelium and form endometrial cups. The invasive trophoblast of the horse has also been investigated by means of ectopic transplantation experiments (Adams and Antczak 2001;Vagnoni et al 1995).…”

Nonhuman primate placental MHC expression: a model for exploring mechanisms of human Maternal-Fetal immune tolerance

“…Although the precise arrangement of maternal and fetal tissues is highly variable, some insight into the maternal response to the placenta is available. In the horse, invasive trophoblasts express polymorphic MHC class I molecules [4] and attract an alloresponse to paternal antigens in the endometrium or after ectopic transplantation [5]. Bovine pregnancy initiated by embryos arising from nuclear transfer (i.e., cloned embryos) is often characterized by fetal growth abnormalities, including altered placental cotyledon number [6].…”