Functions of ectopically transplanted invasive horse trophoblast

Abstract

The invasive and fully antigenic trophoblast of the chorionic girdle portion of the equine fetal membranes has the capacity to survive and differentiate after transplantation to ectopic sites. The objectives of this study were to determine: (i) the survival time of ectopically transplanted allogeneic trophoblast cells in non-pregnant recipient mares, (ii) whether equine Chorionic Gonadotrophin (eCG) can be delivered systemically by transplanted chorionic girdle cells, and (iii) if eCG delivered by the transplanted cells is biologically active and can suppress behavioral signs associated with estrus. Ectopically transplanted chorionic girdle survived for up to 105 days with a mean lifespan of 75 days (95% CI 55–94), and secreted sufficient eCG for the hormone to be measurable in the recipients’ circulation. Immunohistochemical labeling of serial biopsies of the transplant sites and measurement of eCG profiles demonstrated that graft survival was similar to the lifespan of equine endometrial cups in normal horse pregnancy. The eCG secreted by the transplanted cells induced corpora lutea formation and sustained systemic progesterone levels in the recipient mares, effects that are also observed during pregnancy. This in turn caused suppression of estrus behavior in the recipients for up to three months. Thus, ectopically transplanted equine trophoblast provides an unusual example of sustained viability and function of an immunogenic transplant in a recipient with an intact immune system. This model highlights the importance of innate immunoregulatory capabilities of invasive trophoblast cells and describes a new method to deliver sustained circulating concentrations of eCG in non-pregnant mares.

The Equine Endometrial Cup Reaction: A Fetomaternal Signal of Significance

“…Furthermore, immunological sensitization of mares to the MHC antigens of the mating stallion, by skin allografting before establishment of pregnancy, did not reduce the lifespan of the endometrial cups or cause detectable changes in the lymphocyte accumulations (58). The survival time and function of isolated chorionic girdle trophoblast after ectopic transplantation to fully allogeneic, nonpregnant recipient mares suggests that the lifespan of the endometrial cups may be determined primarily by factors intrinsic to the cup cells themselves (59). The invading chorionic girdle cells and early endometrial cup cells are clearly immunogenic.…”

Clinical presentation, treatment and possible causes of persistent endometrial cups illustrated by two cases

“…The quantitative measurement of eCG was determined in duplicate using a solid phase enzyme immunoassay (ELISA) in the microplate format (DRG PMSG ELISA) 5 as described by the manufacturer. A reference standard curve (25–800 miu/ml), positive control samples and 2 negative control samples all in duplicate were included in each plate and eCG concentrations extrapolated from the curve as previously described (de Mestre et al . 2011).…”

T‐cell Tolerance to the Developing Equine Conceptus

“…The lifespans of the cup trophoblasts in MHC compatible pregnancies were not extended (Allen et al. 1984), raising the possibility that the lifespan of endometrial cups may be determined by the trophoblast cells themselves, and not limited by a maternal immune response against them (de Mestre et al. 2011).…”

“…In this system invasive, MHC class I‐positive trophoblast cells are transplanted to the vulvar mucosa, where the cells evoke antibody and T‐cells responses in the recipients in very similar fashion to the situation in normal pregnancy (Adams and Antczak 2001). The transplanted trophoblasts survive for up to 105 days and secrete sufficient eCG into the circulation to cause ovulations and corpora lutea formation that prevent the graft recipients from coming into oestrus for 3 months (de Mestre et al. 2011).…”