Annexin A7 Regulates Endometrial Receptivity

Abstract

A limited window of receptivity is a prerequisite of reproductive success. Indispensable receptivity genes include cyclooxygenase 2 (COX2), an enzyme accomplishing formation of prostaglandin E 2 (PGE 2). A powerful regulator of PGE 2 formation is Annexin A7 (ANXA7). The present study thus explored whether ANXA7 impacts on implantation and fertility. Here we show that ANXA7 is expressed in endometrial tissue and increases upon decidual transformation of human endometrial stromal cells (HESCs) in a timedependent manner. Silencing ANXA7 significantly decreased the expression of PRL and IGFBP1, canonical decidual marker genes, but enhances COX2 and PGE 2 levels. Genetic knockout of AnxA7 in mice significantly increases the number of implantation sites and litter sizes. Further, analysis of human endometrial biopsies showed that ANXA7 transcript and protein levels are decreased during the midluteal window of implantation in women suffering from recurrent pregnancy loss (RPL) when compared to subfertile patients. Taken together, the data indicate that ANXA7 has a conserved role in regulating endometrial receptivity and implantation.

Proteome reprogramming of endometrial epithelial cells by human trophectodermal small extracellular vesicles reveals key insights into embryo implantation

“…Upon manual interrogation, we also noted that several of the significantly upregulated proteins in Tsc‐sEV‐treated cells have previously been shown to be involved in implantation (BSG [125], CD44 [126,127], TAGLN2 [95], ANXA2 [128], PFN1) [129], trophoblast invasion (CSTD [130], THBS1 [131], CDCP1 [132], LGALS3) [133], and endometrial receptivity (CLIC4 [134], EGFR) [135]. Amongst the proteins found in higher abundance, 6 proteins (DPP4, ASS1, ANXA4, COTL1, MRPS2, SOD2) are also associated with endometrial receptivity [136].…”

Annexin Animal Models—From Fundamental Principles to Translational Research

“…Enhanced PGE 2 formation upon AnxA7 depletion appears relevant also for implantation and fertility [ 380 ]. In women suffering from recurrent pregnancy loss, decreased AnxA7 levels in endometrial biopsies during the midluteal window of implantation were observed.…”

“…In women suffering from recurrent pregnancy loss, decreased AnxA7 levels in endometrial biopsies during the midluteal window of implantation were observed. This correlated with the viable Anxa7 −/− strain showing significantly increased implantation sites and litter sizes, indicating that ANXA7-mediated regulation of COX-dependent PGE 2 production contributes to regulating endometrial receptivity and implantation [ 380 ].…”

High-frequency electroacupuncture improves endometrial receptivity via regulating cell adhesion molecules and leukemia inhibitory factor / signal transducer and activator of transcription signaling pathway

“…Embryonic implantation is the crucial biological process in the reproduction of mammals, which allows the activated blastocysts to connect with endometrium by ways of localization, adhesion and invasion. Endometrial receptivity is a parameter to describe embryo implantation onto the endometrium, on which a successful pregnancy is depended [ 1–4 ]. Previous studies have shown that administration of ovulation-inducing drugs in the controlled ovarian hyperstimulation (COH) might bring about an interference of endogenous steroids to endometrium physiological regulation, thus affecting the endometrium receptivity within implantation window period, leading to lower rates in clinical pregnancy and higher ones in abortion.…”