Abnormal Expression of Prolyl Oligopeptidase (POP) and Its Catalytic Products Ac-SDKP Contributes to the Ovarian Fibrosis Change in Polycystic Ovary Syndrome (PCOS) Mice

• Published in: Biomedicines Vol. 11; no. 7; p. 1927
• Main Authors: Han, Suo, Wang, Shimeng, Fan, Xiang, Chen, Mengchi, Wang, Xiaojie, Huang, Yingtong, Zhang, Hongdan, Ma, Yinyin, Wang, Jing, Zhang, Chunping
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.07.2023; MDPI
• Subjects: Alzheimer's disease; Dehydroepiandrosterone; Endocrine disorders; Extracellular matrix; Fibrosis; Gelatinase A; Granulosa cells; Hormones; Hyaluronic acid; Infertility; Kinases; Laboratory animals; Liver; Matrix metalloproteinase; Metabolic syndrome; MMP2; N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP); Oligopeptidase; Olive oil; Ovaries; Ovulation; Plasmids; Polycystic ovary syndrome; polycystic ovary syndrome (PCOS); Prolyl oligopeptidase; prolyl oligopeptidase (POP); Serine proteinase; Testosterone; TGF-β1; Transforming growth factor-b1; Vagina; Beijing China; United States > US; China; TGF-β1; N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP); fibrosis; prolyl oligopeptidase (POP); MMP2; polycystic ovary syndrome (PCOS)
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11071927

Polycystic ovary syndrome (PCOS) is an endocrine disorder and metabolic syndrome. Ovarian fibrosis pathological change in PCOS has gradually attracted people's attention. In this study, we constructed a PCOS mouse model through the use of 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 product. Studies show that abnormal expression and activity of POP and Ac-SDKP are closely related to tissue fibrosis. It was found that the expression of POP and Ac-SDKP was decreased in the 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-β1) 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-β1 in granulosa cells. POP overexpression and Ac-SDKP treatment inhibited the effect of testosterone on TGF-β1 and MMP2 in vitro and inhibited ovarian fibrosis in the PCOS mouse model. In conclusion, PCOS ovarian tissue showed obvious fibrosis. Low expression of POP and Ac-SDKP and changes in fibrotic factors contribute to the ovarian pathological fibrosis induced by androgen.