2. Academic Validation
  3. Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome

Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome

  • Front Biosci (Landmark Ed). 2025 May 22;30(5):38078. doi: 10.31083/FBL38078.
Jiayu Huang 1 2 3,  Yin Tian 2,  Xuemei Liu 2 4,  Zixin Xu 5,  Chong Li 2,  Ling Zhu 2,  Xiru Liu 1,  Jiying Hou 6,  Jingyu Li 2
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
  • 2 Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine, NHC Key Laboratory of Birth Defects and Reproductive Health, Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, 400016 Chongqing, China.
  • 3 The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
  • 4 Molecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, 400016 Chongqing, China.
  • 5 Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, 113-8655 Tokyo, Japan.
  • 6 Faculty of Basic Medical Sciences, Chongqing Medical and Pharmaceutical College, 401331 Chongqing, China.
PMID: 40464508 DOI: 10.31083/FBL38078
Abstract

Background: Polycystic ovary syndrome (PCOS) has increasingly emerged as a significant cause of impaired reproductive outcomes, primarily characterized by a combination of ovulatory dysfunction and decreased oocyte quality. However, the molecular mechanisms underlying the decreased oocyte quality caused by PCOS and preventative strategies still require further investigation.

Method: All procedures were approved by the Animal Ethics Committee of Chongqing Medical University. We established a mice model of PCOS using dehydroepiandrosterone (DHEA) treatment. The estrous cycle was recorded, and plasma sex hormone and trimethylamine N-oxide (TMAO) levels were measured. Ovarian indices and follicular formation were compared. Time-lapse imaging was used to observe in vitro maturation and blastocyst formation. Reactive Oxygen Species (ROS), MitoSOX level, and mitochondrial membrane potential were measured to analyze the mitochondrial function of oocytes. Confocal laser scanning microscopy was used to detect spindle function and chromosomes.

Results: Our study found that DHEA-induced PCOS mice exhibited significantly lower plasma TMAO levels compared to normal mice. Consequently, we supplemented TMAO in PCOS mice and found that the abnormal estrous cycle and reduced ovarian function induced by PCOS could be restored. Additionally, TMAO rescued PCOS-induced defects in oocyte maturation, spindle and chromosome morphology, and embryonic developmental potential. Mechanically, we found that TMAO effectively reduced ROS levels by improving mitochondrial function in PCOS oocytes.

Conclusion: Our findings indicate that the reduction in TMAO levels induced by PCOS may be a key factor influencing reproductive outcomes. TMAO supplementation in vivo can effectively enhance mitochondrial function and oocyte quality in PCOS, holding significant clinical importance for improving assisted reproductive outcomes in patients with PCOS.

Keywords

dehydroepiandrosterone; mitochondria; oocytes; polycystic ovary syndrome; reactive oxygen species; trimethylamine.

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