FASEB Journal · Dec 31, 2025
The Mechanism of Action of NMN in Inhibiting NLRP3 Acetylation-Mediated Granulosa Cell Pyroptosis to Improve Ovarian Reserve Function in Ionizing Radiation-Exposed Mice
By Xue H, Lei S, Wang Q et al.
Ionizing radiation (IR) is well documented for its gonadotoxic effects, resulting in ovarian dysfunction and infertility through direct cellular damage and inflammatory processes. The activation and regulation of the NOD-like receptor protein 3 (NLRP3) inflammasome are crucial for modulating pyroptosis and inflammatory responses. Recent findings suggest that acetylation is essential for the full activation of the NLRP3 inflammasome. This study examines the protective effects of Nicotinamide mononucleotide (NMN) against IR-induced pyroptosis in ovarian granulosa cells, with a particular focus on the molecular mechanisms involving NLRP3 protein acetylation. Our observations from both in vivo and in vitro experiments demonstrate that IR exposure results in increased pyroptosis of granulosa cells, evidenced by elevated levels of NLRP3, Caspase-1, IL-1β, and IL-18, alongside a reduction in ovarian reserve. Importantly, SIRT3, an NAD⁺-dependent deacetylase, plays a role in mitigating the decline in ovarian function by promoting the deacetylation of NLRP3 at lysine 570, thereby inhibiting the activation of the NLRP3 inflammasome. This study provides valuable insights into the potential of NMN supplementation in mitigating the adverse effects of radiation on ovarian function.