%R doi:10.1126/sciadv.abc7409
%X 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.
%P eabc7409
%L uneatlantico107
%D 2021
%T Inhibition of the NLRP3 inflammasome prevents ovarian aging
%V 7
%A José Manuel Navarro-Pando
%A Elísabet Alcocer-Gómez
%A Beatriz Castejón-Vega
%A Elena Navarro-Villarán
%A Mónica Condés-Hervás
%A María Mundi-Roldan
%A Jordi Muntané
%A Antonio J. Pérez-Pulido
%A Pedro Bullon
%A Chun Wang
%A Hal M. Hoffman
%A Alberto Sanz
%A Gabriel Mbalaviele
%A Bernhard Ryffel
%A Mario D. Cordero
%J Science Advances
%N 1