炎症体
不育
生育率
卵巢
激素
内分泌学
内科学
卵巢储备
医学
炎症
生理学
生物
怀孕
遗传学
环境卫生
人口
作者
José M. Navarro‐Pando,Elísabet Alcocer‐Gómez,Beatriz Castejón‐Vega,Jordi Muntané,Pedro Bullón,Chun Wang,Hal M. Hoffman,Alberto Sanz,Gabriel Mbalaviele,Bernhard Ryffel,Mario D. Cordero
标识
DOI:10.1101/2020.04.26.062646
摘要
Inflammation is a hallmark of many processes during aging and reproductive physiology, negatively affecting female fertility. The goal of this study was to 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 female WT mice during reproductive aging. High expression of NLRP3, caspase 1 and IL-1β was also observed in granulosa cells from patients with primary ovarian insufficiency. Ablation of the NLRP3 inflammasome improved the survival and pregnancy rates in mice, increased hormonal levels of AMH, a biochemical marker of ovarian reserve, and autophagy rates in ovarian tissue. Deficiency of the NLRP3 inflammasome 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.
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