PMID- 33959757 OWN - NLM STAT- MEDLINE DCOM- 20211223 LR - 20211223 IS - 1529-7268 (Electronic) IS - 0006-3363 (Linking) VI - 105 IP - 2 DP - 2021 Aug 3 TI - C1QTNF6 participates in the pathogenesis of PCOS by affecting the inflammatory response of granulosa cellsdouble dagger. PG - 427-438 LID - 10.1093/biolre/ioab094 [doi] AB - 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 (TNFalpha) were increased, while the opposite effects were observed when C1QTNF6 was down-regulated in PCOS mice. Furthermore, C1QTNF6 overexpression up-regulated the levels of TNFalpha, IL6, and CRP and activated the AKT/NF-kappaB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-kappaB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-kappaB signaling pathway. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Yan, Sisi AU - Yan S AD - Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China. FAU - Ding, Jinli AU - Ding J AD - Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China. FAU - Zhang, Yi AU - Zhang Y AD - Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China. FAU - Wang, Jiayu AU - Wang J AD - Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China. FAU - Zhang, Sainan AU - Zhang S AD - Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China. FAU - Yin, Tailang AU - Yin T AD - Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China. FAU - Yang, Jing AU - Yang J AD - Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (C1qTNF6 protein, human) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Collagen/*genetics/metabolism MH - Female MH - Granulosa Cells/pathology MH - Humans MH - Inflammation/*genetics MH - Mice MH - Polycystic Ovary Syndrome/genetics/*immunology OTO - NOTNLM OT - C1QTNF6 OT - PCOS OT - granulosa cells OT - inflammation EDAT- 2021/05/08 06:00 MHDA- 2021/12/24 06:00 CRDT- 2021/05/07 07:18 PHST- 2021/01/17 00:00 [received] PHST- 2021/03/31 00:00 [revised] PHST- 2021/04/29 00:00 [accepted] PHST- 2021/05/08 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2021/05/07 07:18 [entrez] AID - 6270855 [pii] AID - 10.1093/biolre/ioab094 [doi] PST - ppublish SO - Biol Reprod. 2021 Aug 3;105(2):427-438. doi: 10.1093/biolre/ioab094.