Seminal plasma (SP) induces a rapid transforming growth factor beta 1 (TGFβ1)-independent up-regulation of epithelial-mesenchymal transdifferentiation (EMT) and myofibroblastic metaplasia-markers in endometriotic (EM) and endometrial cells

Arch Gynecol Obstet. 2019 Jan;299(1):173-183. doi: 10.1007/s00404-018-4965-4. Epub 2018 Nov 19.

Abstract

Purpose: To study if short-term exposure (2 h and 6 h) of endometrial/endometriotic tissues and cells to 10% seminal plasma (SP) can induce EMT/metaplasia.

Methods: Basic research experimental study was carried out in a University hospital-based fertility center. Semen samples, peritoneal fluid (PF) from endometriosis patients, endometrial biopsy from premenopausal women, immortalized endometriotic epithelial cell line (12Z), and immortalized endometrial stromal cell line (St-T1b) were studied. Rapid stain identification test (RSID), TGFβ1 immunofluorescence of washed sperms, TGFβ1-ELISA of SP and PF, in vitro study (2 h and 6 h incubation) and real-time PCR of endometrial tissue and cell lines to analyze gene expression of EMT/metaplasia markers and mediators were done.

Results: SP is still detectable in washed semen. TGFβ1 was expressed on the plasma membrane of the sperms and was significantly more concentrated in SP (88.17 ng/ml) than PF. 10% SP induced an up-regulation of alpha smooth muscle actin expression in endometrial tissue (p = 0.008) and in 12Z cells (p = 0.05), mostly TGFβ1-independent. TWIST expression was persistently significantly down-regulated while Snail1 and 2 were up-regulated, though insignificant.

Conclusion: Our results provide novel evidence to support that even in semen washed twice, SP is still detectable. The changes in EMT/metaplasia markers and mediators give a new insight into a possible effect of SP on the pathogenesis of endometriosis.

Keywords: EMT; Endometriosis; Metaplasia; Seminal plasma; TGFβ1.

MeSH terms

  • Ascitic Fluid / metabolism
  • Biomarkers / metabolism
  • Cell Proliferation
  • Cell Transdifferentiation*
  • Endometriosis / metabolism
  • Endometriosis / pathology*
  • Endometrium / pathology
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Metaplasia
  • Semen / physiology*
  • Stromal Cells / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation

Substances

  • Biomarkers
  • TGFB1 protein, human
  • Transforming Growth Factor beta1