Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells

Yue Ma ¹, Weihua Nong ², Ou Zhong ¹

⁰Institute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China Hengyang, 421001, Hunan, China.

Journal of Ovarian Research +

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November 27, 2024

View abstract on PubMed

Summary

Nicotinamide mononucleotide (NMN) shows promise in treating premature ovarian insufficiency (POI) by reducing inflammation and improving ovarian function. This study demonstrates NMN

Area Of Science

Reproductive Biology
Cellular Biology
Pharmacology

Background

Premature ovarian insufficiency (POI) is a significant clinical challenge with no effective treatments.
NLRP3 inflammasome-induced pyroptosis is a suspected mechanism underlying POI.
Nicotinamide mononucleotide (NMN) exhibits anti-inflammatory properties, suggesting therapeutic potential for POI.

Purpose Of The Study

To investigate the therapeutic effect of NMN on cyclophosphamide (CTX)-induced POI in a rat model.
To elucidate the underlying mechanism of NMN in mitigating POI, focusing on NLRP3 inflammasome-mediated pyroptosis.
To evaluate NMN's impact on ovarian reserve, hormone levels, and inflammatory markers in POI.

Main Methods

POI was induced in Sprague Dawley rats using cyclophosphamide (CTX).
NMN was administered to POI rats, and outcomes were compared to control and saline-treated groups.
In vitro studies assessed NMN's effects on pyroptosis, Nicotinamide adenine dinucleotide (NAD+) levels, and inflammatory cytokines (IL-18, IL-1β) in cell cultures.

Main Results

NMN treatment improved serum hormone levels, follicle count, ovarian reserve, and ovarian index in POI rats.
NMN increased NAD+ levels and SIRT2 expression, leading to reduced expression of NLRP3, Gasdermin D (GSDMD), Caspase-1, IL-18, and IL-1β in ovarian tissue.
In vitro experiments confirmed NMN's ability to inhibit pyroptosis and reduce inflammatory cytokine release.

Conclusions

NMN effectively ameliorates CTX-induced POI in rats by suppressing NLRP3-mediated pyroptosis.
NMN presents a novel therapeutic strategy and potential drug target for clinical management of POI.
The findings highlight the role of NAD+ metabolism and SIRT2 activation in NMN's protective effects against POI.

Keywords:

Nicotinamide mononucleotide Premature ovarian insufficiency Pyroptosis

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