Inhibition of the NLRP3 inflammasome prevents ovarian aging
- Creators
- Navarro Pando, José Manuel
- Alcocer-Gómez, Elísabet
- Castejón Vega, Beatriz
- Navarro Villarán, Elena
- Condés Hervás, Mónica
- Mundi Roldán, María
- Muntané Relat, Jordi
- Pérez Pulido, Antonio J.
- Bullon, Pedro
- Wang, Chun
- Hoffman, Hal M.
- Sanz Montero, Alberto
- Mbalaviele, Gabriel
- Ryffel, Bernhard
- Cordero, Mario D.
Description
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
Additional details
- URL
- https://idus.us.es/handle//11441/136435
- URN
- urn:oai:idus.us.es:11441/136435
- Origin repository
- USE