Endometrial decidualization: of mice and men

Abstract

In murine and human pregnancies, embryos implant by attaching to the luminal epithelium and invading into the stroma of the endometrium. Under the influence of the steroid hormones estrogen and progesterone, the stromal cells surrounding the implanting embryo undergo a remarkable transformation event. This process, known as decidualization, is an essential prerequisite for implantation. It comprises morphogenetic, biochemical, and vascular changes driven by the estrogen and progesterone receptors. The development of mutant mouse models lacking these receptors has firmly established the necessity of steroid signaling for decidualization. Genomic profiling of mouse and human endometrium has uncovered a complex yet highly conserved network of steroid-regulated genes that supports decidualization. To advance our understanding of the mechanisms regulating implantation and better address the clinical challenges of infertility and endometrial diseases such as endometriosis, it is important to integrate the information gained from the mouse and human models.

Figure 1. The molecular pathways controlling decidualization

An emerging blueprint of the molecular pathways underlying the mouse and human endometrial functions, leading to decidualization, is shown. EPI and STR represent uterine epithelial and stromal compartments, respectively. The bold arrows represent the hypothetical linear relationships between the indicated factors. The dashed arrows point to functional links for which the mechanisms are still unknown. The schematic describes only those factors that are discussed in this article. BMP2. Bone morphogenetic protein 2; cAMP, cyclic adenosine monophosphate; C/EBPβ, CCAAT enhancer binding protein-β; COUP-TFII, chicken ovalbumin upstream promoter-transcription factor II; Cx43, connexin 43; E, estrogen; ER, estrogen receptor; FoxO1, Forkhead box O1; Hoxa-10, Homeobox A-10; Ihh, Indian hedgehog; IL, interleukin; IL11Rα, interleukin receptor α, PR, progesterone receptor; VEGF, vascular endothelial growth factor; Wnt4, Wingless 4; PROLIF, proliferation; DIFF, differentiation; ANGIO, angiogenesis.