Dataset Information

BCAA insufficiencies lead 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 (FSH). 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 C57 B6 mice. A mechanism study revealed that the BCAA insufficiency induced POI is associated with abnormal activation of the ceramide-ROS axis and consequent impairment of ovarian granulosa cell function. Significantly, 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.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jin Li

PROVIDER: PXD037353 | iProX | Thu Oct 13 00:00:00 BST 2022

REPOSITORIES: iProX

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BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS.

Guo Xiao X Zhu Yuemeng Y Guo Lu L Qi Yiwen Y Liu Xiaocheng X Wang Jinhui J Zhang Jiangtao J Cui Linlin L Shi Yueyang Y Wang Qichu Q Liu Cenxi C Lu Guangxing G Liu Yilian Y Li Tao T Hong Shangyu S Qin Yingying Y Xiong Xuelian X Wu Hao H Huang Lin L Huang He H Gu Chao C Li Bin B Li Jin J

EMBO molecular medicine 20230227 4

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 bran ...[more]

PMID: 36847712

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Project description:The assembly of the developmentally arrested primordial follicle and subsequent transition to the primary follicle are poorly understood processes critical to ovarian biology. Abnormal primordial follicle development can lead to pathologies such as premature ovarian failure. The current study used a genome-wide expression profile to investigate primordial follicle assembly and development. Rat ovaries with predominantly unassembled, primordial, or primary follicles were obtained. RNA from these ovaries was hybridized to rat microarray gene chips, and the gene expression (i.e., ovarian transcriptome) was compared between the developmental stages. Analysis of the ovarian transcriptome demonstrated 148 genes up-regulated and 50 genes down-regulated between the unassembled and primordial follicle stages. Observations demonstrate 80 genes up-regulated and 44 genes down-regulated between the primordial and primary follicle stages. The analysis demonstrated 2332 genes common among the three developmental stages, 146 genes specific for the unassembled follicles, 94 genes specific for the primordial follicles, and 151 genes specific for the primary follicles. Steroidogenic genes are up-regulated between unassembled and primordial follicles, and then many are again down-regulated between primordial and primary follicles. The hormones inhibin and Mullerian inhibitory substance (MIS) display a similar pattern of expression with the highest levels of mRNA in the primordial follicles. Several novel unknown genes that had dramatic changes in expression during primordial follicle development were also identified. Gene families/clusters identified that were up-regulated from unassembled to primordial follicles include growth factors and signal transduction gene clusters, whereas a down-regulated gene family was the synaptonemal complex genes associated with meiosis. Gene families/clusters that were up-regulated between primordial and primary follicles included immune response genes, metabolic enzymes, and proteases, whereas down-regulated gene families include the globulin genes and some steroidogenic genes. The expression of several growth factors changed during primordial follicle development, including vascular endothelial growth factor and insulin-like growth factor II. Elucidation of how these changes in gene expression coordinate primordial follicle assembly and the primordial to primary follicle transition provides a better understanding of these critical biological processes and allows selection of candidate regulatory factors for further investigation. Experiment Overall Design: RNA samples from two control groups (pooled untreated cultured ovaries) are compared to two treated groups (pooled cultured ovaries treated with progesterone)

Dataset Information

BCAA insufficiencies lead to premature ovarian insufficiency via ceramide induced elevation of ROS

Publications

BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS.

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