TY  - JOUR
AV  - public
A1  - Navarro-Pando, José Manuel
A1  - Alcocer-Gómez, Elísabet
A1  - Castejón-Vega, Beatriz
A1  - Navarro-Villarán, Elena
A1  - Condés-Hervás, Mónica
A1  - Mundi-Roldan, María
A1  - Muntané, Jordi
A1  - Pérez-Pulido, Antonio J.
A1  - Bullon, Pedro
A1  - Wang, Chun
A1  - Hoffman, Hal M.
A1  - Sanz, Alberto
A1  - Mbalaviele, Gabriel
A1  - Ryffel, Bernhard
A1  - Cordero, Mario D.
TI  - Inhibition of the NLRP3 inflammasome prevents ovarian aging
ID  - uneatlantico107
UR  - http://doi.org/10.1126/sciadv.abc7409
SN  - 2375-2548
VL  - 7
IS  - 1
Y1  - 2021/01//
N2  - 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-1? 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.
JF  - Science Advances
ER  -