Inhibition of the NLRP3 inflammasome prevents ovarian aging

José M. Navarro-Pando, Elísabet Alcocer-Gómez, Beatriz Castejón-Vega, Elena Navarro-Villarán, Mónica Condés-Hervás, María Mundi-Roldan, Jordi Muntané, Antonio J. Pérez-Pulido, Pedro Bullon, Chun Wang, Hal M. Hoffman, Alberto Sanz, Gabriel Mbalaviele, Bernhard Ryffel, Mario D. Cordero

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Inflammation is a hallmark of aging and is negatively affecting female fertility. In this study, we 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 WT mice during reproductive aging. High expression of NLRP3, caspase-1, and IL-1β was also observed in granulosa cells from patients with ovarian insufficiency. Ablation of NLRP3 improved the survival and pregnancy rates and increased anti-Müllerian hormone levels and autophagy rates in ovaries. Deficiency of NLRP3 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.

Original languageEnglish
Article numbereabc7409
JournalScience Advances
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2021

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