Nicotinamide Mononucleotide Improves Endometrial Homeostasis in a Rat Model of Polycystic Ovary Syndrome by Decreasing Insulin Resistance and Regulating the Glylytic Pathway

Wenhui Zhang; Jiaming Zhang; Haoxuan Xue; Xi Chen; Meixiang Li; Shenghua Chen; Zhiling Li; Leonardo Antonio Sechi; Qian Wang; Giampiero Capobianco; Xiaocan Lei

doi:10.1002/mnfr.202400340

Nicotinamide Mononucleotide Improves Endometrial Homeostasis in a Rat Model of Polycystic Ovary Syndrome by Decreasing Insulin Resistance and Regulating the Glylytic Pathway

Mol Nutr Food Res. 2024 Oct 17:e2400340. doi: 10.1002/mnfr.202400340. Online ahead of print.

Authors

Wenhui Zhang^{1

2}, Jiaming Zhang¹, Haoxuan Xue^{1

2}, Xi Chen², Meixiang Li², Shenghua Chen², Zhiling Li³, Leonardo Antonio Sechi^{4

5}, Qian Wang^{1

3

4

6}, Giampiero Capobianco⁶, Xiaocan Lei²

Affiliations

¹ Gynecology & Obstetrics and Reproductive Medical Center, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, China.
² Institute of Applied Anatomy and Reproductive Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, China.
³ Reproductive Center, The First Affiliated Hospital of Shantou University Medical College, Shantou University, Shantou, 515041, China.
⁴ Department of Biomedical Sciences, University of Sassari, Sassari, 07100, Italy.
⁵ Unit of Microbiology and Virology, AOU Sassari, Sassari, 07100, Italy.
⁶ Gynecologic and Obstetric Clinic, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, 07100, Italy.

PMID: 39420767
DOI: 10.1002/mnfr.202400340

Abstract

Scope: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that can lead to insulin resistance (IR) and dysregulation of glucose metabolism, resulting in an imbalance in the endometrial environment, which is unfavorable for embryo implantation of PCOS. This study aims to investigate whether nicotinamide mononucleotide (NMN) improves the stability of the endometrium in a rat model of PCOS and identifies whether it is related to reduce IR and increase glycolysis levels and its potential signaling pathway.

Methods and results: Female Sprague-Dawley (SD) rats are fed letrozole and a high-fat diet (HFD) to form the PCOS model, then the model rats are treated with or without NMN. It randomly divided into control, PCOS, and PCOS-NMN groups according to the feeding and treating method. Compared with the PCOS group, the regular estrous cycles are restored, the serum androgen (p<0.01) and fasting insulin levels (p<0.05) are reduced, and endometrial morphology (p<0.05) is improved in NMN-PCOS group. Furthermore, NMN inhibits endometrial cell apoptosis, improves endometrial decidualization transition, reduces IR, restores the expression of glycolysis rate-limiting enzymes, and activates the PI3K/AKT pathway in the uterus.

Conclusions: These results suggest that NMN enhances endometrial tissue homeostasis by decreasing uterine IR and regulating the glycolysis through the PI3K/AKT pathway.

Keywords: PI3K/AKT pathway; endometrial homeostasis; glycolysis; insulin resistance; nicotinamide mononucleotide; polycystic ovary syndrome.

Abstract

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