Navarro-Pando, Jose MAlcocer-Gomez, ElísabetCastejon-Vega, BeatrizNavarro-Villaran, ElenaCondes-Hervas, MonicaMundi-Roldan, MariaMuntane, JordiPerez-Pulido, Antonio JBullon, PedroWang, ChunHoffman, Hal MSanz, AlbertoMbalaviele, GabrielRyffel, BernhardCordero, Mario D2023-02-092023-02-092020-11-09Navarro-Pando JM, Alcocer-Gómez E, Castejón-Vega B, Navarro-Villarán E, Condés-Hervás M, Mundi-Roldan M, et al. Inhibition of the NLRP3 inflammasome prevents ovarian aging. Sci Adv. 2021 Jan 1;7(1):eabc7409http://hdl.handle.net/10668/17079Inflammation 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.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/InflammasomesNLR family, pyrin domain-containing 3 proteinCaspase 1Pregnancy rateMCC-950InfertilityFertilityInflammationOvarian diseasesAgingInterleukin-1AutophagyGranulosa cellsEstradiolresearch article33523841open accessAutofagiaCélulas de la granulosaEnfermedades del ovarioEnvejecimientoEstradiolFertilidadInfertilidadInflamaciónInterleucina-110.1126/sciadv.abc74092375-2548PMC7775749https://doi.org/10.1126/sciadv.abc7409https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775749/pdf