Transforming growth factor beta1 from endometriomas promotes fibrosis in surrounding ovarian tissues via Smad2/3 signaling†

Abstract

To elucidate whether the endometriotic cells of endometriomas synthesize transforming growth factor beta1 (TGF-beta1) and understand how it affects surrounding ovarian tissue. We collected biopsies of the cystic walls from 42 endometriomas and 29 mature teratomas and compared mRNA and protein expression of fibrosis-related factors between the cystic walls. Then we detected TGFB1 mRNA synthesis in endometriomas, and tested TGF-beta1 fibrotic effect in vitro. Moreover, we verified the expression of Smad2/3 signaling components in the endometriotic cystic wall in order to understand whether TGF-beta1/Smad signaling is involved in fibrosis formation of the tissue surrounding endometriomas. The cystic walls from endometriomas demonstrated severe adhesion to ovarian tissue and obvious fibrosis compared with the mature teratomas, which was proven by the increased mRNA expression of fibrotic markers. Additionally, TGFB1 was obviously expressed in the endometriotic cystic wall, and total TGFB1 protein was significantly higher in the cystic walls of endometriomas than mature teratomas. Interestingly, TGFB1 mRNA was confirmed to be specifically synthesized in the endometriotic loci through fluorescence in situ hybridization. Cultured endometriomas derived stromal cells showed obvious fibrosis after exposed to TGF-beta1. Furthermore, components of the TGF-beta1/Smad pathway such as Smad2, Smad3, Smad4, and their phosphorylated forms were also expressed in the same location as TGF-beta1, TGF-beta receptor1, and fibrotic factors expressed in the endometriotic cystic walls. In summary, endometriotic cells of endometriomas synthesize TGF-beta1 leading to fibrosis and adhesion to ovarian tissues, and TGF-beta1/Smad signaling pathway is involved in this pathological process.

Retrospective evaluation of pathological results among women with ovarian endometriomas versus teratomas

“…Moreover, varying degrees of hypermethylation of SNRPN gene and KvDMR but not H19DMR locus were found in the presence of maternal uniparental disomy in several cystic teratomas of the ovary examined (38). Recently, in a study aiming to shed light on the mechanism regarding how endometriomas become more adherent to ovarian tissues compared with teratomas, it was found that the cystic walls of endometriomas exhibited obvious fibrosis compared with mature teratomas and endometriotic cells synthesized TGF-β1, a critical factor that promotes fibrosis formation (39).…”

MiR-210-3p protects endometriotic cells from oxidative stress-induced cell cycle arrest by targeting BARD1

“…Fluorescence in situ hybridisation (FISH) analysis was performed in five normal endometrium and five paired eutopic and ectopic tissues according to standard methods 31 . An oligonucleotide probe complementary to miR-210-3p was purchased from Guangzhou Exon Biotechnology Co. Ltd (Guangzhou, China).…”

Baicalein inhibits FURIN‐MT1‐MMP‐mediated invasion of ectopic endometrial stromal cells in endometriosis possibly by reducing the secretion of TGFB1

“…TGFB1, a pleiotropic cytokine, is crucial to the development of EMs. Accumulating evidence has confirmed that the expression of TGFB1 is increased in the peritoneal fluid, 18,19 ectopic endometrium, 18,[20][21][22] and peripheral blood 23 of patients with EMs compared with healthy individuals. TGFB1 is involved in epithelial-mesenchymal transition (EMT) and Fibroblast-Myo-fibroblast transition (FMT) and also provides a favorable microenvironment for survival of ectopic cells which have successfully implanted in a new site through regulation of angiogenesis and increasing the secretion of proinflammatory cytokines.…”