TGF-β1 in Seminal Plasma Promotes Endometrial Mesenchymal Stem Cell Growth via p42/44 and Akt Pathway in Patients With or Without Endometriosis

Reprod Sci. 2022 Mar;29(3):723-733. doi: 10.1007/s43032-021-00562-x. Epub 2022 Jan 3.

Abstract

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 that may promote endometrial tissue survival. Here, 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). Proliferation, cell foci formation, cell cycle progression, and growth marker expression of E- and NE-MSCs were promoted by SP. These effects may be mediated through activation of transforming growth factor beta 1 (TGF-β1), Akt, and p42/44 signaling, which enhances CDK2 and CDK6 expression and accelerates cell cycle progression. Xenografts exposed to SP exhibited a three-fold increase in volume and four-fold increase in weight after 14 days. Our findings demonstrate that TGF-β1 in SP may promote endometrial tissue survival which will allow us to understand the pathogenesis and develop novel approaches for prevention and therapies of endometriosis.

Keywords: Endometriosis; Mesenchymal stem cells; Proliferation; Seminal plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Biomarkers / metabolism
  • Cell Cycle / physiology
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Endometriosis / metabolism*
  • Endometriosis / pathology
  • Endometrium / cytology*
  • Female
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Semen / chemistry*
  • Signal Transduction
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Biomarkers
  • Cytokines
  • Transforming Growth Factor beta1
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases