Local glucose elevation activates pyroptosis via NLRP3 inflammasome in ovarian granulosa cells of overweight patients. Issue 3 (24th February 2023)

• Record Type: Journal Article
• Authors: Xu, Rui; Zhao, Hanting; Qi, Jia; Yao, Guangxin; He, Yaqiong; Lu, Yao; Zhu, Qinling; Wang, Yuan; Ding, Ying; Zhu, Zhenyi; Li, Xinyu; Vankelecom, Hugo; Sun, Yun
• Is Part Of: FASEB journal. Volume 37:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-24
• Subjects: granulosa cells -- high‐glucose -- NLRP3 inflammasome -- overweight -- pyroptosis; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202201796RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Overweight, with an increasing prevalence worldwide, significantly impairs the clinical outcomes following in vitro fertilization (IVF). Hyperglycemia, hyperlipidemia, and metabolic disorders are always accompanied by the majority of overweight patients. The association between granulosa cell function and metabolic alterations in follicular fluid including lipids, proteins, and growth factors has been extensively documented. However, the effects of higher glucose level on ovarian granulosa cells (GCs), remain largely unknown. In this study, we identified that overweight women had elevated follicular glucose level which profoundly activated NLRP3 inflammasome and pyroptosis. An in vitro correlation between follicular high glucose, NLRP3 inflammasome and pyroptosis was also established. More importantly, in granulosa cells of overweight patients, the activation of the NLRP3 inflammasome and pyroptosis induced by high glucose was involved in the dysregulation of estradiol synthesis. Our study may provide new options to interpretate and improve IVF outcomes in overweight women. Abstract : Elevated glucose in the follicular fluid negatively regulates estradiol synthesis via activating NLRP3 inflammasome and pyroptosis in the granulosa cells of overweight female patients.