Paradoxical role of phosphorylated STAT3 in normal fertility and the pathogenesis of adenomyosis and endometriosis

Abstract

Signal transducer and activator of transcription 3 (STAT3), when phosphorylated at tyrosine 705, plays an important role in endometrial stromal cell decidualization and the receptivity of the endometrial epithelium during embryo implantation. However, the function of phosphorylated STAT3 (p-STAT3) in normal uterine receptivity is distinct from that in adenomyosis and endometriosis. In normal pregnancy, STAT3 phosphorylation in the endometrial epithelium determines the success of embryo implantation by regulating uterine receptivity. Additionally, p-STAT3 promotes cellular proliferation and differentiation during endometrial decidualization, which is crucial for embryonic development. In contrast, excessive STAT3 phosphorylation occurs in adenomyosis and endometriosis, which may lead to disease progression. Therefore, achieving a delicate balance in STAT3 activation is crucial. This review aimed to focus on the current understanding and knowledge gaps regarding the control of p-STAT3 activity in normal and pathological endometrial processes. This topic is important because precise control of p-STAT3 production could alleviate the symptoms of adenomyosis and endometriosis, improve endometrial receptivity, and potentially mitigate infertility without compromising normal fertility processes.

DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation

“…5C). Notably, these are key TFs that regulate stemness and differentiation programs, in the breast but also male and female reproductive tissues (Chang et al, 2013; Hu et al, 2011; Huang et al; Jorgez et al, 2021; Murashima et al, 2015; Xu et al, 2023) stratified epithelial tissues (Barbieri and Pietenpol, 2006; Craig et al, 2023; Fang et al, 2020; Portal et al, 2022; Wu et al, 2003), and the hematopoietic system (Delgado and León, 2010; Huang et al, 2014; Kortylewski et al, 2005; Pant et al, 2012; Shimizu and Yamamoto, 2023; Trikha et al, 2011). Input of these transcription factor hits into STRINGDB, a database and visualizer of known protein-protein interactions (Szklarczyk et al, 2022) shows that these proteins form a closely related network, with each of these proteins only being 1-2 interactions away from each other (Supplemental Fig.…”

“…5C). Notably, these are key TFs that regulate stemness and differentiation programs, in the breast but also male and female reproductive tissues (Chang et al, 2013;Hu et al, 2011;Jorgez et al, 2021;Murashima et al, 2015;Xu et al, 2023) stratified epithelial tissues (Barbieri and Pietenpol, 2006;Craig et al, 2023;Fang et al, 2020;Portal et al, 2022;Wu et al, 2003), and the hematopoietic system (Delgado and León, 2010; (which was not certified by peer review) is the author/funder. All rights reserved.…”