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10 November 2017 Transforming growth factor beta1 from endometriomas promotes fibrosis in surrounding ovarian tissues via Smad2/3 signaling
Li Bing Shi, Feng Zhou, Hai Yan Zhu, Dong Huang, Xiao Ying Jin, Chao Li, Yongdong Dai, Yi Bin Pan, Song Ying Zhang
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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 cysticwalls from 42 endometriomas and 29mature teratomas and compared mRNA and protein expression of fibrosis-related factors between the cysticwalls. 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.

Summary Sentence

Prospectively analyzing cystic walls from excised ovarian endometriomas and mature teratomas, we demonstrated that TGF-beta1 is specifically expressed in endometriomas and promotes fibrosis in surrounding ovarian tissues via Smad2/3 signaling.

© The Author(s) 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Li Bing Shi, Feng Zhou, Hai Yan Zhu, Dong Huang, Xiao Ying Jin, Chao Li, Yongdong Dai, Yi Bin Pan, and Song Ying Zhang "Transforming growth factor beta1 from endometriomas promotes fibrosis in surrounding ovarian tissues via Smad2/3 signaling," Biology of Reproduction 97(6), 873-882, (10 November 2017). https://doi.org/10.1093/biolre/iox140
Received: 16 February 2017; Accepted: 9 November 2017; Published: 10 November 2017
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