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Spring
(2023-03-31 13:10):
#paper doi: 10.15252/emmm.202317450
EMBO Molecular Medicine[IF:14.26]
① 纳入两个独立的队列人群，比较了早发性卵巢功能不全（POI）女性血清代谢组学，发现其表现为支链氨基酸（BCAA）不足相关的代谢紊乱；② 在小鼠模型中，低BCAA饮食干预使年轻小鼠出现POI样的代谢、内分泌、卵巢和生殖变化；③ 细胞实验表明，BCAA不足会上调神经酰胺，诱导ROS升高，从而使卵巢颗粒细胞功能受损；④ 有趣的是，BCAA膳食补充可以阻止雌性小鼠ROS诱导的POI发展，提示其预防价值。
BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS
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 …
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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.
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