Uterine receptivity and the plasma membrane transformation

Abstract

This review begins with a brief commentary on the diversity of placentation mechanisms, and then goes on to examine the extensive alterations which occur in the plasma membrane of uterine epithelial cells during early pregnancy across species. Ultrastructural, biochemical and more general morphological data reveal that strikingly common phenomena occur in this plasma membrane during early pregnancy despite the diversity of placental types-from epitheliochorial to hemochorial, which ultimately form in different species. To encapsulate the concept that common morphological and molecular alterations occur across species, that they are found basolaterally as well as apically, and that moreover they are an ongoing process during much of early pregnancy, not just an event at the time attachment, the term 'plasma membrane transformation' is suggested which also emphasises that alterations in this plasma membrane during early pregnancy are key to uterine receptivity. INTRODUCTIONContact between the plasma membrane of uterine epithelial cells and that of the trophoblast is a common beginning to implantation in most species studied so far. This is perhaps not surprising since uterine epithelial cells are the first site of contact between maternal and foetal tissue at the beginning of blastocyst attachment and implantation. The similarities in these early events of the uterine response during early pregnancy and placentation however, go further than mere contact between opposing surfaces. A now considerable body of evidence indicates that the behaviour of the plasma membrane of the uterine epithelial cells during early pregnancy has many common aspects across species ranging from viviparous lizards to human beings and that moreover, these similarities exist regardless of the placental type which ultimately develops. This review pays special attention to events at the cellular level in uterine epithelial cells and to the plasma membrane in particular, but does so within the wider context of uterine receptivity for implantation across species.

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

“…3,[42][43][44] In the present study, using multiple genetic and cellular approaches combined with uterine conditional Rac1 depletion mouse model, we demonstrated that uterine Rac1 via Pak1-ERM signaling cascade ensures normal luminal epithelial integrity conducive to on-time embryo implantation. We also provided evidence that TNFα-Rac1-P38 signaling cascade is essential for uterine luminal epithelium elimination during postimplantation uterine development ( Figure 9).…”

“…44 The columnar luminal epithelium transits to cuboidal shape and microvilli on the apical plasma show a retraction which makes the apical plasma more flat. [44][45][46][47] Moreover, tight junction molecules, such as Occludin, ZO-1 and Claudins are dynamically expressed in the periimplantation uterus.…”

“…44 The columnar luminal epithelium transits to cuboidal shape and microvilli on the apical plasma show a retraction which makes the apical plasma more flat. [44][45][46][47] Moreover, tight junction molecules, such as Occludin, ZO-1 and Claudins are dynamically expressed in the periimplantation uterus. 48,49 This timely remodeling of junction complexes under the control of ovarian steroid hormones represents a decreased epithelial apicalbasal polarity during uterine receptivity establishment.…”

Embryo implantation evolved from an ancestral inflammatory attachment reaction

“…Implantation involves the apposition, attachment, and, in many species, the invasion of the blastocyst into the uterus (1). In particular, structural and molecular changes occur in the luminal epithelia that allow the embryo to attach and invade the uterus (2). Epithelial changes are followed by remodeling of the endometrial stroma, generally known as "decidualization," i.e., the transformation of endometrial stromal fibroblasts into decidual stromal cells, as well as modifications of the endometrial vascular bed (3).…”

Lgr4 is required for endometrial receptivity acquired through ovarian hormone signaling

“…3(E)) In contrast, the expression of ERα target genes (ltf, muc1) was significantly higher in Lgr4 K5 KO . [14][15][16] However, the phosphorylation level of Ser-118 and Ser-104/106 of ERα was not elevated in Lgr4 K5 KO luminal cells, indicating that other phosphorylation sites of ERα might have been affected by the LGR4 deletion (Supplemental Fig. 1).…”