Minireview: Steroid-Regulated Paracrine Mechanisms Controlling Implantation

Abstract

Implantation is an essential process during establishment of pregnancy in mammals. It is initiated with the attachment of the blastocyst to a receptive uterine epithelium followed by its invasion into the stromal tissue. These events are profoundly regulated by the steroid hormones 17β-estradiol and progesterone. During the past several years, mouse models harboring conditional gene knockout mutations have become powerful tools for determining the functional roles of cellular factors involved in various aspects of implantation biology. Studies using these genetic models as well as primary cultures of human endometrial cells have established that the estrogen receptor α, the progesterone receptor, and their downstream target genes critically regulate uterine growth and differentiation, which in turn control embryo-endometrial interactions during early pregnancy. These studies have uncovered a diverse array of molecular cues, which are produced under the influence of estrogen receptor α and progesterone receptor and exchanged between the epithelial and stromal compartments of the uterus during the progressive phases of implantation. These paracrine signals are critical for acquisition of uterine receptivity and functional interactions with the embryo. This review highlights recent work describing paracrine mechanisms that govern steroid-regulated uterine epithelial-stromal dialogue during implantation and their roles in fertility and disease.

Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization

“…PR knockout mice also display compromised decidualization and obviously with the absence of polyploidy. 36 The results presented here found stromal cells cultured with HB-EGF produced an increased number of polyploid cells. HB-EGF is an early molecular marker of embryo-uterine cross-talk during implantation and regulated by progesterone.…”

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

“…8). To investigate whether the subfertility observed in the uterine GR KO mice was due to deficient estrogen and progesterone signaling, adrenalectomized/ovariectomized control and uterine GR KO mice were treated with E 2 or P4, and the estrogendependent induction of uterine weight (24 h postinjection) and target gene expression (4 h postinjection) were analyzed.…”

The p160/Steroid Receptor Coactivator Family: Potent Arbiters of Uterine Physiology and Dysfunction1

“…These responses can be modulated at multiple levels that regulate normal physiology but can also contribute to disease when they become dysfunctional. Although tremendous progress has been attained in disclosing crucial steroid hormone signaling pathways in uterine physiologic and pathophysiologic contexts; reviewed previously [2][3][4][5], the identity of the pivotal coregulators (coactivators or corepressors) that operate in these signaling scenarios remains elusive. Given coregulators in general are potent modulators of a tissue's transcriptional response to both intracellular and extracellular physiologic signals [6,7], identifying which of these transcriptional coregulators is required for a given uterine response constitutes a critical underpinning for future advances in our mechanistic understanding of hormone-dependent uterine biology and pathobiology.…”