EMBO Molecular Medicine (Apr 2023)
BCAA insufficiency leads to premature ovarian insufficiency via ceramide‐induced elevation of ROS
- Xiao Guo,
- Yuemeng Zhu,
- Lu Guo,
- Yiwen Qi,
- Xiaocheng Liu,
- Jinhui Wang,
- Jiangtao Zhang,
- Linlin Cui,
- Yueyang Shi,
- Qichu Wang,
- Cenxi Liu,
- Guangxing Lu,
- Yilian Liu,
- Tao Li,
- Shangyu Hong,
- Yingying Qin,
- Xuelian Xiong,
- Hao Wu,
- Lin Huang,
- He Huang,
- Chao Gu,
- Bin Li,
- Jin Li
Affiliations
- Xiao Guo
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Yuemeng Zhu
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Lu Guo
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Yiwen Qi
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Xiaocheng Liu
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Jinhui Wang
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Jiangtao Zhang
- Center for Reproductive Medicine, Cheeloo College of Medicine Shandong University Jinan China
- Linlin Cui
- Center for Reproductive Medicine, Cheeloo College of Medicine Shandong University Jinan China
- Yueyang Shi
- Shandong Provincial Hospital, Cheeloo College of Medicine Shandong University Jinan China
- Qichu Wang
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Cenxi Liu
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Guangxing Lu
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Yilian Liu
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Tao Li
- Shandong Provincial Hospital, Cheeloo College of Medicine Shandong University Jinan China
- Shangyu Hong
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Yingying Qin
- Shanghai First Maternity and Infant Hospital Shanghai China
- Xuelian Xiong
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Hao Wu
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Lin Huang
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- He Huang
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Chao Gu
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Bin Li
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- Jin Li
- Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital and Institute of Metabolism and Integrative Biology Fudan University Shanghai China
- DOI
- https://doi.org/10.15252/emmm.202317450
- Journal volume & issue
-
Vol. 15,
no. 4
pp. n/a – n/a
Abstract
Abstract Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle‐stimulating hormone. Though POI affects many aspects of women's health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch‐chain amino acid (BCAA) insufficiency‐related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57BL/6J mice. A mechanism study revealed that the BCAA insufficiency‐induced POI is associated with abnormal activation of the ceramide‐reactive oxygen species (ROS) axis and consequent impairment of ovarian granulosa cell function. Significantly, the dietary supplement of BCAA prevented the development of ROS‐induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI.
Keywords