Eph–ephrin A system regulates murine blastocyst attachment and spreading

Abstract

Although numerous adhesion molecules are expressed on mammalian endometrial epithelial cells, there have not been any studies of a mechanism to prevent premature attachment of the embryo. In this study, we examined the possible involvement of Eph-ephrin interaction, which can induce repulsive forces. In mice, Eph A1, A2, and A4 were expressed on endometrial epithelial cells and ephrin A1-4 on blastocysts. Reverse transcriptase-polymerase chain reaction showed that mRNA expression of ephrin A1-4 on embryos transiently decreased around the implantation period. Immunohistochemistry demonstrated that the expression of Eph A1 on endometrial epithelial cells and ephrin A1 and A3 expression on embryos decreased at implantation sites. Recombinant Eph A1 reacted with cell the surface of ephrin A-bearing trophectoderm cells. Attachment assays using Eph A1-coated dishes showed that blastocyst attachment was reversibly inhibited by Eph A1. These findings suggest an important role of the Eph-ephrin A system in regulating the initial embryo-maternal contact during the cross-talk period that precedes embryo implantation.

Single-cell gene expression of the bovine blastocyst

“…2014), ID2, which is closely related to ID1, participates in regulation of basic helix-loop-helix transcription factors in human placenta (Liu et al . 2004), and interactions between ephrin A and ephrin receptors have been proposed to block premature binding of blastocysts to endometrium (Fujii et al . 2006).…”

Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

“…Between days 9 and 12 of pregnancy, a number of factors that stimulate cellular proliferation, migration, and attachment were upregulated, including connective tissue growth factor (CTGF), ephrin-A1 (EFNA1), ephrin-B1 (EFNB1), GRP, IGFBP1, and LGALS15. The cell(s) expressing EFNA1 and EFNB1 in the ovine uterus are not known, but they are expressed in the epithelia of human and mouse endometria and implicated in blastocyst attachment and spreading (19,20). Both GRP and CTGF are expressed in ovine endometrial GE (28,75).…”

Dysregulated erythropoietin-producing hepatocellular receptor A2 (EphA2) is involved in tubal pregnancy via regulating cell adhesion of the Fallopian tube epithelial cells

“…EphA2 is abundant in human endometrial epithelial cells and its ligand ephrin is expressed in the blastocysts. A previous study revealed that the Eph-ephrin A system could regulate the initial embryo-maternal contact during the cross-talk period that preceded embryo implantation in the endometrium [14]. Similar regulatory mechanism may exist in the process of tubal implantation.…”

“…This leads to the initiation of a downstream signaling cascade, which results in the internalization and degradation of Pho-EphA2 itself [11, 12]. It is found that EphA2 is highly localized in endometrial epithelial cells accompanied by its Ephrin ligand expressed on embryonic trophoblasts, and EphA2 is suggested to mediate the establishment of uterine implantation by regulating embryo-maternal contact [13, 14]. Furthermore, EphA2 can promote the invasion and proliferation of the human extravillous trophoblastic cells probably via regulating the ephrin-A1 ligand [15].…”