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

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.

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.

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.

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. Similar content being viewed by others

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We would like to thank Professor Anna Starzinski-Powitz for supplying the 12Z cell line and Dr. Birgit Gellersen for supplying the St-T1b cell line. Moreover, we appreciate the valuable technical assistance by Mrs. Birgit Pers in the gynecology laboratory and the medical technicians in the andrology laboratory at the Center of Reproductive Medicine and Andrology (CeRA) during the whole study. Author information Authors and Affiliations Contributions MGI study design, data analysis, manuscript drafting, and critical discussion. EA statistical analysis and critical discussion. SS, SK and LK manuscript editing and critical discussion. MV RSID test execution, interpretation, and manuscript critical discussion. MGI, SS and SK, ANS samples collection. MG and ANS shared in the study design, manuscript editing and critical discussion. Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Informed consent All patients included in this study gave written informed consent. The study was approved by the local research and ethics committee of the medical faculty and the regional medical board of Westfalen, Münster (1 IX Greb). Electronic supplementary material Below is the link to the electronic supplementary material. 404_2018_4965_MOESM1_ESM.docx (download DOCX ) Supplementary figure (1): Immunostaining of the 12Z cell line. The epithelial cells express cytokeratin (middle panel) and vimentin (lower panel) but no ASMA (upper panel). Supplementary figure (2): Immunostaining of the St-T1b cell line. The stromal cells express vimentin (lower panel) but neither cytokeratin (middle panel) nor ASMA (upper panel) (DOCX 180 kb) Rights and permissions About this article Cite this article Ibrahim, M.G., Elghonaimy, E.A., Schäfer, S. et al. 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 299, 173–183 (2019). https://doi.org/10.1007/s00404-018-4965-4 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00404-018-4965-4