Local glucose elevation activates pyroptosis via NLRP3 inflammasome in ovarian granulosa cells of overweight patients

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.

Adverse effects of type 2 diabetes mellitus on ovarian reserve and pregnancy outcomes during the assisted reproductive technology process

“…On the other hand, in the hyperglycemic state, a disturbed microenvironment may lead to the apoptosis of granulocytes. As one study has shown that elevated follicular glucose profoundly accelerated the pyroptosis of ovarian granulosa cells, affecting the synthesis of hormones ( 44 ) and AMH secretion. Thus, this may be another important reason for the decline in AMH levels in diabetic patients.…”