{"title":"Untargeted metabolomics reveals homogeneity and heterogeneity between physiological and pathological ovarian aging.","authors":"Lihua Zeng, Yunyi Liang, Lizhi Huang, Zu'ang Li, Manish Kumar, Xiasheng Zheng, Jing Li, Songping Luo, Ling Zhu","doi":"10.1186/s13048-025-01625-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ovarian aging is the main cause of reduced reproductive life span, yet its metabolic profiles remain poorly understood. This study aimed to reveal the metabolic homogeneity and heterogeneity between physiological and pathological ovarian aging.</p><p><strong>Methods: </strong>Seventy serum samples from physiological ovarian aging participants, pathological ovarian aging participants (including diminished ovarian reserve (DOR), subclinical premature ovarian insufficiency (scPOI) and premature ovarian insufficiency (POI)), as well as healthy participants were collected and analyzed by untargeted metabolomics.</p><p><strong>Results: </strong>Five homogeneous differential metabolites (neopterin, menaquinone, sphingomyelin (SM) (d14:1/24:2), SM (d14:0/21:1) and SM (d17:0/25:1)) were found in both physiological and pathological ovarian aging. While five distinct metabolites, including phosphoglyceride (PC) (17:0/18:2), PC (18:2e/17:2), SM (d22:1/14:1), SM (d14:1/20:1) and 4-hydroxyretinoic acid were specific to pathological ovarian aging. Functional annotation of differential metabolites suggested that folate biosynthesis, ubiquinone and other terpenoid-quinone biosynthesis pathways, were mainly involved in the ovarian aging process. Meanwhile, dopaminergic synapses pathway was strongly associated with scPOI, vitamin digestion and absorption and retinol metabolism were associated with POI. Furthermore, testosterone sulfate, SM (d14:0/28:1), PC (18:0e/4:0) and 4-hydroxyretinoic acid, were identified as potential biomarkers for diagnosing physiological ovarian aging, DOR, scPOI, and POI, respectively. Additionally, SM (d14:1/24:2) strongly correlated with both physiological and pathological ovarian aging. 4-hydroxyretinoic acid was strongly correlated with pathological ovarian aging.</p><p><strong>Conclusions: </strong>Metabolic homogeneity of physiological and pathological ovarian aging was related to disorders of lipid, folate, ubiquinone metabolism, while metabolic heterogeneity between them was related to disorders of lipid, vitamin and retinol metabolism.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"56"},"PeriodicalIF":3.8000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912745/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ovarian Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13048-025-01625-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Ovarian aging is the main cause of reduced reproductive life span, yet its metabolic profiles remain poorly understood. This study aimed to reveal the metabolic homogeneity and heterogeneity between physiological and pathological ovarian aging.
Methods: Seventy serum samples from physiological ovarian aging participants, pathological ovarian aging participants (including diminished ovarian reserve (DOR), subclinical premature ovarian insufficiency (scPOI) and premature ovarian insufficiency (POI)), as well as healthy participants were collected and analyzed by untargeted metabolomics.
Results: Five homogeneous differential metabolites (neopterin, menaquinone, sphingomyelin (SM) (d14:1/24:2), SM (d14:0/21:1) and SM (d17:0/25:1)) were found in both physiological and pathological ovarian aging. While five distinct metabolites, including phosphoglyceride (PC) (17:0/18:2), PC (18:2e/17:2), SM (d22:1/14:1), SM (d14:1/20:1) and 4-hydroxyretinoic acid were specific to pathological ovarian aging. Functional annotation of differential metabolites suggested that folate biosynthesis, ubiquinone and other terpenoid-quinone biosynthesis pathways, were mainly involved in the ovarian aging process. Meanwhile, dopaminergic synapses pathway was strongly associated with scPOI, vitamin digestion and absorption and retinol metabolism were associated with POI. Furthermore, testosterone sulfate, SM (d14:0/28:1), PC (18:0e/4:0) and 4-hydroxyretinoic acid, were identified as potential biomarkers for diagnosing physiological ovarian aging, DOR, scPOI, and POI, respectively. Additionally, SM (d14:1/24:2) strongly correlated with both physiological and pathological ovarian aging. 4-hydroxyretinoic acid was strongly correlated with pathological ovarian aging.
Conclusions: Metabolic homogeneity of physiological and pathological ovarian aging was related to disorders of lipid, folate, ubiquinone metabolism, while metabolic heterogeneity between them was related to disorders of lipid, vitamin and retinol metabolism.
期刊介绍：
Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ.
Topical areas include, but are not restricted to:
Ovary development, hormone secretion and regulation
Follicle growth and ovulation
Infertility and Polycystic ovarian syndrome
Regulation of pituitary and other biological functions by ovarian hormones
Ovarian cancer, its prevention, diagnosis and treatment
Drug development and screening
Role of stem cells in ovary development and function.
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