CXCL12 and its receptors regulate granulosa cell apoptosis in PCOS rats and human KGN tumor cells

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  • 1 Reproductive Medicine Center, Wuhan University Zhongnan Hospital, Wuhan, Hubei, People’s Republic of China
  • 2 Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan University Zhongnan Hospital, Wuhan, Hubei, People’s Republic of China
  • 3 Department of Obstetrics and Gynecology, Wuhan University Zhongnan Hospital, Wuhan, Hubei, People’s Republic of China
  • 4 Department of Reproductive Center, First Affliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China

Correspondence should be addressed to Y Zhang; Email: zhangyuanzhen@vip.sina.com

*(L Jin and L Ren contributed equally to this work)

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder accompanied by chronic low-grade inflammation; its etiology is still undefined. This study investigated the expression of CXCL12, CXCR4, and CXCR7 in PCOS rats and their role in regulation of apoptosis. To accomplish this, we established an in vivo PCOS rat model and studied KGN cells (human ovarian granulosa cell line) in vitro. In PCOS rats, the ovarian expression of CXCL12, CXCR4, and CXCR7 was reduced, and the apoptosis rate of granulosa cells was increased, accompanied by decreased expression of BCL2 and increased expression of BAX and cleaved CASPASE3 (CASP3). We further showed that recombinant human CXCL12 treatment upregulated BCL2, downregulated BAX, and cleaved CASP3 in KGN cells to inhibit their apoptosis in a concentration-dependent manner; moreover, the effect of CXCL12 was weakened by CXCR4 antagonist AMD3100 and anti-CXCR7 neutralizing antibody. In conclusion, PCOS rats showed decreased CXCL12, CXCR4, and CXCR7 expression and increased apoptosis rate of ovarian granulosa cells. Further, in human KGN cells, CXCL12 regulated the expression of BAX, BCL2, and cleaved CASP3 to inhibit apoptosis through CXCR4- and CXCR7-mediated signal transmission. These findings may provide a theoretical and practical basis for illuminating the role of proinflammatory cytokines in the pathogenesis of PCOS.

 

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