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

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 decrease...

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Main Authors: Jiayu Huang, Yin Tian, Xuemei Liu, Zixin Xu, Chong Li, Ling Zhu, Xiru Liu, Jiying Hou, Jingyu Li
Format: Article
Language:English
Published: IMR Press 2025-05-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/30/5/10.31083/FBL38078
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author Jiayu Huang
Yin Tian
Xuemei Liu
Zixin Xu
Chong Li
Ling Zhu
Xiru Liu
Jiying Hou
Jingyu Li
author_facet Jiayu Huang
Yin Tian
Xuemei Liu
Zixin Xu
Chong Li
Ling Zhu
Xiru Liu
Jiying Hou
Jingyu Li
author_sort Jiayu Huang
collection DOAJ
description 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.
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spelling doaj-art-e1fb37d3fed54b1086cefddbb1e4d6c22025-08-20T03:25:59ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-05-013053807810.31083/FBL38078S2768-6701(25)01714-9Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary SyndromeJiayu Huang0Yin Tian1Xuemei Liu2Zixin Xu3Chong Li4Ling Zhu5Xiru Liu6Jiying Hou7Jingyu Li8Reproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, ChinaChongqing 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, ChinaChongqing 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, ChinaDepartment of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, 113-8655 Tokyo, JapanChongqing 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, ChinaChongqing 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, ChinaReproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, ChinaFaculty of Basic Medical Sciences, Chongqing Medical and Pharmaceutical College, 401331 Chongqing, ChinaChongqing 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, ChinaBackground: 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.https://www.imrpress.com/journal/FBL/30/5/10.31083/FBL38078polycystic ovary syndrometrimethylaminereactive oxygen speciesoocytesdehydroepiandrosteronemitochondria
spellingShingle Jiayu Huang
Yin Tian
Xuemei Liu
Zixin Xu
Chong Li
Ling Zhu
Xiru Liu
Jiying Hou
Jingyu Li
Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome
Frontiers in Bioscience-Landmark
polycystic ovary syndrome
trimethylamine
reactive oxygen species
oocytes
dehydroepiandrosterone
mitochondria
title Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome
title_full Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome
title_fullStr Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome
title_full_unstemmed Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome
title_short Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome
title_sort trimethylamine n oxide supplementation enhances the quality of oocytes in mice of polycystic ovary syndrome
topic polycystic ovary syndrome
trimethylamine
reactive oxygen species
oocytes
dehydroepiandrosterone
mitochondria
url https://www.imrpress.com/journal/FBL/30/5/10.31083/FBL38078
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