Bisphenol A Exposure Enhances Endometrial Stromal Cell Invasion and Has a Positive Association with Peritoneal Endometriosis

Results of previous epidemiology studies on BPA exposure and endometriosis (EMs) risk were inconsistent, and were limited by inappropriate control selection, incorrect BPA detection method, and the generalization of different subtypes of EMs. Upregulated matrix metalloproteinase (MMP) 2 and MMP9 are involved in the development of EMs. We conducted a case–control study among 120 EMs patients and 100 healthy women to evaluate the relationships between BPA exposure and MMP2, MMP9 expressions, and the risk of EMs subtypes. Besides, we used human endometrial stromal cell lines (HESCs) to investigate the underlying mechanisms. Creatinine-adjusted urinary BPA concentrations were positively correlated with serum MMP2, MMP9 levels, and the risk of peritoneal EMs (third vs lowest quartile: OR 4.92, 95% CI 1.47, 16.50; fourth versus lowest quartile: OR 3.70, 95% CI 1.07, 12.74, Ptrend = 0.030). The risk of peritoneal EMs increased approximately tenfold when creatinine-adjusted urinary BPA concentration was 2 μg/g. In vitro study found that BPA exposure increased MMP2, MMP9 expressions in a dose-dependent manner. The effects of BPA on HESCs could be blocked by G protein-coupled estrogen receptor (GPER) inhibitor or mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibitor. This study provides evidence that BPA exposure promotes peritoneal EMs, and raises a concern about the potential toxicity of BPA on the female reproductive system. Similar content being viewed by others

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Funding This study was supported by a research grant (no. 81771543) from the National Natural Science Foundation of China. Author information Authors and Affiliations Corresponding author Ethics declarations This project was approved by the Ethics Committee of Zhongnan Hospital, Wuhan University. Competing Interests The authors declare that they have no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic Supplementary Material ESM 1 (download DOCX ) (DOCX 556 kb) Rights and permissions About this article Cite this article Wen, X., Xiong, Y., Jin, L. et al. Bisphenol A Exposure Enhances Endometrial Stromal Cell Invasion and Has a Positive Association with Peritoneal Endometriosis. Reprod. Sci. 27, 704–712 (2020). https://doi.org/10.1007/s43032-019-00076-7 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-019-00076-7