Endometrial responses to embryonic signals in the primate

Abstract

The delicate interaction between an embryo and the uterus to initiate implantation and maintain pregnancy is one of the most elegant and fascinating interactions in human biology. Understanding the molecular events of embryo-maternal interaction is of interest to reproductive biologists, clinicians and couples affected by infertility. We have established the baboon as the non-human primate model for studying embryo implantation. Infusion of chorionic gonadotropin (CG), the major embryonic signal of primates, into the uterine cavity of normal cycling baboons during the window of receptivity induces a myriad of morphological, biochemical and molecular changes in the estrogen and progesterone primed endometrium. The luminal epithelium responds by forming plaques, the overall secretory function of the glandular epithelium increases and the stromal response is characterized by induction of α-smooth muscle actin (αSMA). Cross talk between ovarian and embryonic hormones is evidenced by the fact that these responses are inhibited upon treatment with a progesterone receptor antagonist. CG signals principally through the seven transmembrane LH/CG G-protein coupled receptor, and activates a mitogen activated protein kinase pathway in the endometrial epithelium that is unique and independent of all the classical signaling pathways. In the stromal compartment, CG both rescues stromal fibroblasts from their apoptotic demise and also differentiates them into the decidualized phenotype. We propose that stromal cell survival and differentiation is mediated by a critical modulator of cell fate, Notch-1. Thus, CG is an important embryonic signal which modulates communication between the embryo and the endometrium and induces changes that are critical to successful implantation.

Intrauterine injection of human chorionic gonadotropin before embryo transfer significantly improves the implantation and pregnancy rates in in vitro fertilization/intracytoplasmic sperm injection: a prospective randomized study

“…The investigators proved that these responses were inhibited after treatment with progesterone receptor antagonist. It is possible that hCG intrauterine injection before ET, as described in our study, produced the various changes in the endometrium described in the experiments done by Licht et al and Banerjee and Fazleabas (9,21).…”

In vitro Fertilization Outcome following Embryo Transfer with or without Preinstillation of Human Chorionic Gonadotropin into the Uterine Cavity: A Randomized Controlled Trial

“…Wallace et al [13] demonstrated improved pregnancy rates after an intramuscular injection of hCG at ET in cows. In a study by Banerjee and Fazleabas [14], intrauterine injection of hCG in baboons induced a favorable uterine environment for embryo implantation. Although hCG has been commercially available for a long time, a few human trials have addressed the value of hCG injection in ET.…”

“…Intrauterine injection of hCG has been associated with significant pro-implantation changes of the endometrium in primates [14]. Moreover, in a recent study it has been shown that intrauterine injection of hCG before ET improves implantation and pregnancy rates [15].…”

The role of invasive trophoblast in implantation and placentation of primates

“…The signalling pathways controlling plaque formation and decidualization in baboons have been the object of close scrutiny [34]. Decidual cells occur also in the vervet monkey (Chlorocebus aethiops) [35].…”