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) (PMID:33523841) (PMCID:PMC7775749)

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 and Castejon Vega, Dr Beatriz
• 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 > School of Molecular Biosciences
• 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