Abstract
Endometrial cells perceive and respond to their microenvironment forming the basis of endometrial homeostasis. Errors in endometrial cell signaling are responsible for a wide spectrum of endometrial pathologies ranging from infertility to cancer. Intensive research over the years has been decoding the sophisticated molecular means by which endometrial cells communicate to each other and with the embryo. The objective of this review is to provide the scientific community with the first overview of key endometrial cell signaling pathways operating throughout the menstrual cycle. On this basis, a comprehensive and critical assessment of the literature was performed to provide the tools for the authorship of this narrative review summarizing the pivotal components and signaling cascades operating during seven endometrial cell fate “routes”: proliferation, decidualization, implantation, migration, breakdown, regeneration, and angiogenesis. Albeit schematically presented as separate transit routes in a subway network and narrated in a distinct fashion, the majority of the time these routes overlap or occur simultaneously within endometrial cells. This review facilitates identification of novel trajectories of research in endometrial cellular communication and signaling. The meticulous study of endometrial signaling pathways potentiates both the discovery of novel therapeutic targets to tackle disease and vanguard fertility approaches.
Highlights
Endometrial cells perceive and respond to their microenvironment forming the basis of endometrial homeostasis
Upon binding of WNT ligands, the activation of disheveled blocks the destruction of the complex and β-catenin accumulates in the cytoplasm and can translocate to the nucleus to interact with members of the TCF/LEF transcription factor family, to regulate the expression of genes associated with proliferation and survival such as cyclin D1 and c-MYC [45,46]
In this manner the fast acting cyclic adenosine monophosphate (cAMP) sensitizes stromal cells to the slow-acting P4, which will act through progesterone receptor (PR) in a genomic or nongenomic manner to inhibit epithelial cell proliferation and stimulate differentiation of stromal cells. cAMP is contributing to the cell cycle regulation by inducing the transcription of p53, a tumor suppressor protein, arresting endometrial cells at G2/M checkpoint [74]
Summary
The compound adjective “highly dynamic” is a cliché when it comes to portraying the endometrium. The tissue itself is stratified into two layers: the functional, a superficial transient layer adjacent to the uterine cavity, and the basal, a deeper permanent layer adjacent to the myometrium. The thickness of the tissue is determined by its functional layer, which changes throughout the menstrual cycle according to hormonal influences [2]. The phases of the menstrual cycle are defined on the basis of phenomena occurring during the ovarian cycle as the follicular phase (day 0 to day 13), the ovulation (day 14) and the luteal phase (day 15 to day 28). Considering the endometrial cycle phenomena this time round, these phases would rather be the menses (day 0 to day 5), the proliferative phase (day 6 to day 13) and the secretory phase. FigFuigreur1e. 1E.nEdnodmometertirailacl eclelllsisgignnaalilninggnneettwwoorrkk iilllluussttrraatteeddaassaassuubbwwaayymmapapshsohwowinigngthtehseesveevnernouroteustes opoepraetreadtedbybyddififffeerreenntt mmoolleeccuulleess, ,nanrarrartaetdeidn tihnetrheevireewv.iTewF i.n TblFueinbobxleusedbenooxteess tdraennsoctreispttiroannfsaccrtioprtsi.on facAtollrsa.bbArellviaabtibornesvaiaretioexnpsaanrdeedexipnatnhedemdaiinn ttehxet. mThaeinX tmexatr.k TinhteheXremdacrikrcilen itnhdeicraeteds cpirrocgleesitnedroicnaetes prowgiethstderraownealw. ithdrawal
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