Inhibition of the NLRP3 inflammasome prevents ovarian aging

Navarro-Pando, J. M. et al. (2021) Inhibition of the NLRP3 inflammasome prevents ovarian aging. Science Advances, 7(1), eabc7409. (doi: 10.1126/sciadv.abc7409)

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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.

Item Type:Articles
Additional Information:This study was supported by a grant from the Andalusian regional government (Grupo de Investigacion Junta de Andalucia CTS113, Consejería de Salud de la Junta de Andalucia: PI-0036-2014) and European funding in Region Centre-Val de Loire (FEDER N° 2016-00110366 BIO-TARGET and EX005756 BIO-TARGET II). G.M. is supported by NIH/NIAMS AR068972 and AR076758 grants.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sanz Montero, Professor Alberto
Authors: Navarro-Pando, J. M., Alcocer-Gómez, E., Castejón-Vega, B., Navarro-Villarán, E., Condés-Hervás, M., Mundi-Roldan, M., Muntané, J., Pérez-Pulido, A. J., Bullon, P., Wang, C., Hoffman, H. M., Sanz, A., Mbalaviele, G., Ryffel, B., and Cordero, M. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
ISSN:2375-2548
ISSN (Online):2375-2548
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Science Advances 7(1): eabc7409
Publisher Policy:Reproduced under a Creative Commons License

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