C1QTNF6 participates in the pathogenesis of PCOS by affecting the inflammatory response of granulosa cells

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor-alpha (TNF alpha) were increased, while the opposite effects were observed when C1QTNF6was down-regulated in PCOS mice. Furthermore, C1QTNF6 overexpression up-regulated the levels of TNF alpha, IL6, and CRP and activated the AKT/NF-kappa B pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-kappa B inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pa kappa B signaling pathway.

Automated summary

The study found that C1QTNF6 expression was significantly elevated in the serum and GCs of PCOS patients, as well as in the serum and ovaries of PCOS mouse models. C1QTNF6 can regulate inflammation and activate the inflammatory response through the AKT/NF-κB pathway.