TGF-β1 in Seminal Plasma Promotes Endometrial Mesenchymal Stem Cell Growth via p42/44 and Akt Pathway in Endometriosis

Abstract

Background: The cause of endometriosis, which is characterized by the existence of functional endometrial tissue outside the uterine cavity, is poorly understood. Seminal plasma (SP) is rich in multiple cytokines may promote endometrial tissue survival. Methods: We evaluated the effect of SP on growth of endometrial mesenchymal stem cells (MSCs) from women with endometriosis (E-MSCs), and women without endometriosis (NE-MSCs). Additionally, effects of SP on endometriotic implants were analyzed using a xenograft model of endometriosis in immunodeficient nude mice.Results: Proliferation, cell foci formation, cell cycle progression, and growth marker expression of E- and NE-MSCs were promoted by SP. SP significantly stimulated phosphorylation of p42/44 and Akt and increased expression of the proliferation marker in E- and NE-MSCs, which was attenuated by transforming growth factor beta 1 (TGF-β1) receptor inhibitor SB431542, Akt inhibitor LY294002, or p42/44 MAPK inhibitor PD98059. SP enhanced CDK2 and CDK6 expression and accelerated cell cycle progression in E-MSCs. Xenografts exposed to SP exhibited a three-fold increase in volume and four-fold increase in weight after 14 days.Conclusions: Our findings demonstrate that TGF-β1 in SP may promote endometrial tissue survival. These effects may be mediated through activation of TGF-β1, Akt, and p42/44 signaling, which enhances CDK2 and CDK6 expression and accelerates cell cycle progression.