2. Academic Validation
  3. The Mechanism of Action of NMN in Inhibiting NLRP3 Acetylation-Mediated Granulosa Cell Pyroptosis to Improve Ovarian Reserve Function in Ionizing Radiation-Exposed Mice

The Mechanism of Action of NMN in Inhibiting NLRP3 Acetylation-Mediated Granulosa Cell Pyroptosis to Improve Ovarian Reserve Function in Ionizing Radiation-Exposed Mice

  • FASEB J. 2025 Dec 31;39(24):e71335. doi: 10.1096/fj.202503167R.
Haoxuan Xue 1,  Siyuan Lei 1,  Qian Wang 1 2 3 4,  Weihua Nong 5,  Zhihan Zhang 1,  Yanhong Wei 5,  Qiumei Huang 5,  Jiameng Yang 1,  Yanxuan Tan 1,  Xiaocan Lei 1
Affiliations

Affiliations

  • 1 Clinical Anatomy and Reproductive Medicine Application Institute, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
  • 2 Gynecologic and Obstetric Clinic, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy.
  • 3 Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
  • 4 Reproductive Center, The First Affiliated Hospital of Shantou University Medical College, Shantou University, Shantou, China.
  • 5 Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Department of Obstetrics and Gynecology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
PMID: 41395774 DOI: 10.1096/fj.202503167R
Abstract

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.

Keywords

Acetylation; Ionizing radiation; NLRP3; Ovarian reserve; Pyroptosis.

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