Physiological and molecular determinants of embryo implantation

Abstract

Embryo implantation involves the intimate interaction between an implantation-competent blastocyst and a receptive uterus, which occurs in a limited time period known as the window of implantation. Emerging evidence shows that defects originating during embryo implantation induce ripple effects with adverse consequences on later gestation events, highlighting the significance of this event for pregnancy success. Although a multitude of cellular events and molecular pathways involved in embryo-uterine crosstalk during implantation have been identified through gene expression studies and genetically engineered mouse models, a comprehensive understanding of the nature of embryo implantation is still missing. This review focuses on recent progress with particular attention to physiological and molecular determinants of blastocyst activation, uterine receptivity, blastocyst attachment and uterine decidualization. A better understanding of underlying mechanisms governing embryo implantation should generate new strategies to rectify implantation failure and improve pregnancy rates in women.

The bovine endometrial epithelial cells promote the differentiation of trophoblast stem-like cells to binucleate trophoblast cells

“…3 Coculture of bEECs with bTS cells. Similar to bovine imEECs, the bovine EECs established in this study expressed both an epithelial marker, cytokeratin, and a stromal marker, vimentin (Zhang et al 2013). The acquisition of vimentin by cytokeratin-positive epithelial cells during in vitro culture periods has been reported (Bergh et al 1984;Wang et al 2000;Zeiler et al 2007), which has been explained by a limited epithelial to mesenchymal transition (EMT; Pagan et al 1996).…”

“…Therefore, the development of in vitro models is required to study implantation processes. Bovine endometrial epithelial cells (EECs) are often used as a bovine in vitro model for studying the biological characteristics, cellular and molecular mechanisms, and responses to infection or damage of the bovine uterine epithelium, as well as for investigating the impacts of bovine embryo implantation and development of interactions between the embryo and mother (Bai et al 2014;Fortier et al 1988;Hou et al 2015;Skarzynski et al 2000;Zhang et al 2013). Coculture of bovine EECs and bovine trophoblast cells can be used to investigate the maturation of trophoblasts and the formation of binucleate cells.…”

Hmgn1 acts downstream of C/EBPβ to regulate the decidualization of uterine stromal cells in mice

“…1,2 Following the onset of embryo implantation, uterine stromal cells surrounding the implanting embryo undergo extensive proliferation and subsequent differentiation into Polyploid decidual cells (decidualization). 2,3 Proper decidualization is essential for continued embryonic development within the uterus and achieving successful pregnancy, because impaired decidualization can lead to miscarriage or even pathological pregnancy such as preeclampsia or intrauterine growth restriction. 2,4 Genome-wide microarray analyses have identified a number of genes that are up-regulated or down-regulated during decidualization, suggesting the presence of complex mechanisms of gene expression.…”

Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice

“…During this period, the acquisition of blastocyst implantation competency is synchronized with the establishment of uterine receptivity. [4][5][6] On the basis of previous findings, uterine sensitivity to implantationcompetent blastocysts is classically divided into three stages: pre-receptive, receptive and refractory phases. 7 In mice, prior to day 4 of pregnancy, the uterus is conventionally considered as the pre-receptive phase.…”