TNFAIP3 Reduction-of-Function Drives Female Infertility and CNS Inflammation.

ABSTRACT: Women with autoimmune and inflammatory aetiologies can exhibit reduced fecundity. TNFAIP3 is a master negative regulator of inflammation, and has been linked to many inflammatory conditions by genome wide associations studies, however its role in fertility remains unknown. Here we show that mice harbouring a mild Tnfaip3 reduction-of-function coding variant (Tnfaip3 ^I325N) that reduces the threshold for inflammatory NF-κB activation, exhibit reduced fecundity. Sub-fertility in Tnfaip3 ^I325N mice is associated with irregular estrous cycling, low numbers of ovarian secondary follicles, impaired mammary gland development and insulin resistance. These pathological features are associated with infertility in human subjects. Transplantation of

SUBMITTER: Zammit NW 

PROVIDER: S-EPMC9027572 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature