Inhibition of the NLRP3 inflammasome prevents ovarian aging

Abstract

Inflammation is a hallmark of many processes during aging and reproductive physiology, negatively affecting female fertility. The goal of this study was to evaluate the role of the NLRP3 inflammasome in ovarian aging and female fertility. Age-dependent increased expression of NLRP3 in the ovary was observed in female WT mice during reproductive aging. High expression of NLRP3, caspase 1 and IL-1β was also observed in granulosa cells from patients with primary ovarian insufficiency. Ablation of the NLRP3 inflammasome improved the survival and pregnancy rates in mice, increased hormonal levels of AMH, a biochemical marker of ovarian reserve, and autophagy rates in ovarian tissue. Deficiency of the NLRP3 inflammasome also reduced serum FSH and estradiol levels. Consistent with these results, pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved fertility in female mice to levels comparable to those of Nlrp3−/− mice. These results suggest that the NLRP3 inflammasome is implicated in the age-dependent loss of female fertility and position this inflammasome as a potential new therapeutic target for the treatment of infertility.

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging

“…This is also the case in the ovaries. Recent studies have shown that inflammation is a key marker of the aging ovarian stroma and is considered a new mechanism of POI (Huang et al, 2019b; Navarro-Pando et al, 2020 ). Clinical studies in humans have shown that inflammatory marker levels are associated with the risk of POI or early menopause.…”