Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study
Abstract Background Early diagnosis and early delivery are the main strategies for the treatment of premature ovarian insufficiency (POI). However, POI warning markers, especially those that can be detected through noninvasive methods, are very limited; therefore, the identification of noninvasive m...
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BMC
2025-06-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-025-01696-1 |
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| author | Hangjing Tan Jing Zhao Baisheng Wang Yanping Li |
| author_facet | Hangjing Tan Jing Zhao Baisheng Wang Yanping Li |
| author_sort | Hangjing Tan |
| collection | DOAJ |
| description | Abstract Background Early diagnosis and early delivery are the main strategies for the treatment of premature ovarian insufficiency (POI). However, POI warning markers, especially those that can be detected through noninvasive methods, are very limited; therefore, the identification of noninvasive markers for POI is urgent. Methods We acquired POI GWAS summary statistics from the FinnGen database. The metabolome, circulating plasma proteins, gut microbiota, immunophenotypes, circulating microRNAs (miRNAs), and two proteomes were obtained for two-sample Mendelian randomization (MR). Specifically, we employed inverse variance weighted (IVW) as the main method to calculate the MR effect estimates. eQTL data (from the eQTLGen Consortium) were employed for SMR. Hub genes were identified using the String database and Cytoscape software. Potential mechanisms of POI were identified via pathway enrichment analysis of the identified genes and miRNAs. Results Three metabolites (sphinganine-1-phosphate levels, X-23636 levels, 4-methyl-2-oxopentanoate levels), two circulating plasma proteins (fibroblast growth factor 23 levels, neurotrophin-3 levels), one gut microbiota (faecalibacterium abundance), one immunophenotype (HVEM on naive CD8 + T cells), 23 miRNAs (miR-500a-3p, miR-555, miR-584-5p, miR-642a-5p, miR-671-3p, miR-1324, miR-6870-3p, miR-1468-5p, miR-146a-3p, miR-221-3p, miR-3121-5p, miR-3184-3p, miR-3185, miR-335-5p, miR-4302, miR-4506, miR-6808-5p, miR-6894-5p, miR-145-5p, miR-149-3p, miR-23a-3p, miR-3141, and miR-374b-5p), and three hub genes (ESR1, ERBB2, and GART) serve as warning markers for POI. Enrichment analysis indicated that pathways such as glutathione metabolism and the PI3 kinase pathway may be involved in mechanisms regulating POI. Conclusion Our results are the first to identify noninvasive predictors for POI via MR, providing contributions for early warning and fertility guidance for clinical POI patients. |
| format | Article |
| id | doaj-art-4ff5b04c43ae4717bef6a48a8e2241ea |
| institution | OA Journals |
| issn | 1757-2215 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj-art-4ff5b04c43ae4717bef6a48a8e2241ea2025-08-20T02:07:41ZengBMCJournal of Ovarian Research1757-22152025-06-011811910.1186/s13048-025-01696-1Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation studyHangjing Tan0Jing Zhao1Baisheng Wang2Yanping Li3Department of Reproductive Medicine, Xiangya Hospital, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityHunan Key Laboratory of Oral Health Research, Xiangya School of Stomatology, Central South UniversityDepartment of Reproductive Medicine, Xiangya Hospital, Central South UniversityAbstract Background Early diagnosis and early delivery are the main strategies for the treatment of premature ovarian insufficiency (POI). However, POI warning markers, especially those that can be detected through noninvasive methods, are very limited; therefore, the identification of noninvasive markers for POI is urgent. Methods We acquired POI GWAS summary statistics from the FinnGen database. The metabolome, circulating plasma proteins, gut microbiota, immunophenotypes, circulating microRNAs (miRNAs), and two proteomes were obtained for two-sample Mendelian randomization (MR). Specifically, we employed inverse variance weighted (IVW) as the main method to calculate the MR effect estimates. eQTL data (from the eQTLGen Consortium) were employed for SMR. Hub genes were identified using the String database and Cytoscape software. Potential mechanisms of POI were identified via pathway enrichment analysis of the identified genes and miRNAs. Results Three metabolites (sphinganine-1-phosphate levels, X-23636 levels, 4-methyl-2-oxopentanoate levels), two circulating plasma proteins (fibroblast growth factor 23 levels, neurotrophin-3 levels), one gut microbiota (faecalibacterium abundance), one immunophenotype (HVEM on naive CD8 + T cells), 23 miRNAs (miR-500a-3p, miR-555, miR-584-5p, miR-642a-5p, miR-671-3p, miR-1324, miR-6870-3p, miR-1468-5p, miR-146a-3p, miR-221-3p, miR-3121-5p, miR-3184-3p, miR-3185, miR-335-5p, miR-4302, miR-4506, miR-6808-5p, miR-6894-5p, miR-145-5p, miR-149-3p, miR-23a-3p, miR-3141, and miR-374b-5p), and three hub genes (ESR1, ERBB2, and GART) serve as warning markers for POI. Enrichment analysis indicated that pathways such as glutathione metabolism and the PI3 kinase pathway may be involved in mechanisms regulating POI. Conclusion Our results are the first to identify noninvasive predictors for POI via MR, providing contributions for early warning and fertility guidance for clinical POI patients.https://doi.org/10.1186/s13048-025-01696-1Premature ovarian insufficiencyGenome-wide association studyMendelian randomizationNon-invasiveBiomarkers |
| spellingShingle | Hangjing Tan Jing Zhao Baisheng Wang Yanping Li Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study Journal of Ovarian Research Premature ovarian insufficiency Genome-wide association study Mendelian randomization Non-invasive Biomarkers |
| title | Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study |
| title_full | Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study |
| title_fullStr | Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study |
| title_full_unstemmed | Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study |
| title_short | Noninvasive markers for warning premature ovarian insufficiency: a Mendelian randomisation study |
| title_sort | noninvasive markers for warning premature ovarian insufficiency a mendelian randomisation study |
| topic | Premature ovarian insufficiency Genome-wide association study Mendelian randomization Non-invasive Biomarkers |
| url | https://doi.org/10.1186/s13048-025-01696-1 |
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