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bioRxiv · 10.1101/2023.01.04.522712

Abnormal expression of Prolyl oligopeptidase (POP) and its catalytic products Ac-SDKP contributes to the ovarian fibrosis change in Polycystic ovary syndrome (PCOS) mice

Han, S.·Wang, S.·Fan, X.·Wang, X.·Huang, Y.·Zhang, H.·Ma, Y.·Wang, J.·Zhang, C.
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Abstract

Polycystic ovary syndrome (PCOS) is an endocrine disorder and metabolic syndrome. Ovarian fibrosis pathological change in PCOS gradually attracted peoples attention. In this study, we constructed PCOS mice model through dehydroepiandrosterone. Sirius red staining showed that the ovarian tissues in PCOS mice had obvious fibrosis. Prolyl oligopeptidase(POP) is a serine protease and N-acetyl-Seryl-aspartyl-Lysyl-proline (Ac-SDKP) is its catalytic products. Studies show that abnormal expression and activity of POP and Ac-SDKP are closely related to tissue fibrosis. We found that the expression of POP and Ac-SDKP was decreased in ovaries of PCOS mice. Further studies showed that POP and Ac-SDKP promoted the expression of Matrix metalloproteinases 2 (MMP-2) expression and decreased the expression of transforming growth factor beta 1 (TGF-{beta}1) in granulosa cells. Hyperandrogenemia is a typical symptom of PCOS. We found that testosterone induced the low expression of POP and MMP2, and high expression of TGF-{beta}1 in granulosa cells. POP overexpression and Ac-SDKP treatment inhibited the effect of testosterone on TGF-{beta}1 and MMP2 in vitro and ovarian fibrosis in PCOS mice model. In conclusion, PCOS ovarian tissue showed obvious fibrosis. Low expression of POP, Ac-SDKP and changes in fibrotic factors contribute to the ovarian pathological fibrosis induced by androgen.

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Han, S., Wang, S., Fan, X., Wang, X., Huang, Y., Zhang, H., Ma, Y., Wang, J., Zhang, C.. 2023-01-04. Abnormal expression of Prolyl oligopeptidase (POP) and its catalytic products Ac-SDKP contributes to the ovarian fibrosis change in Polycystic ovary syndrome (PCOS) mice. https://doi.org/10.1101/2023.01.04.522712

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