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Background <p>Age-related diminished ovarian reserve (DOR) exhibits marked significant individual variation. Some women of advanced age with normal ovarian reserve (NOR) achieve better reproductive outcomes than age-matched DOR patients.</p> Objective <p>This study aimed to compare the metabolomic and proteomic profiles of follicular fluid (FF) from advanced maternal age(AMA) women with DOR and NOR, to reveal differences in the follicular microenvironment and identify potential biomarkers and related pathways.</p> Methods <p>LC-MS/MS was employed to profile metabolites and proteins in FF samples from both groups. Differentially expressed metabolites (DEMs) and differentially expressed proteins (DEPs) were identified using multivariate and univariate statistical analyses. Functional annotation and pathway enrichment analyses were performed using the GO and KEGG databases. Metabolomic and proteomic data were analyzed using bioinformatic approaches to identify key molecules and potential biomarkers associated with DOR.</p> Results <p>Untargeted metabolomic analysis identified a total of 89 DEMs, including 32 upregulated and 57 downregulated. Data-independent acquisition (DIA) quantitative proteomic analysis identified 335 DEPs, of which 40 were up-regulated and 295 were down-regulated. Multi-omics analysis revealed significant alterations in several pathways in DOR patients, including metabolic pathways, cholesterol metabolism, alanine, aspartate and glutamate metabolism, carbon metabolism, central carbon metabolism in cancer, and sulfur metabolism. Based on protein expression profiles associated with these dysregulated pathways, four candidate protein biomarkers were further identified.</p> Conclusions <p>Based on proteomic and metabolomic analyses, this study systematically characterized the follicular microenvironment of AMA with different ovarian reserve. A series of key DEPs and DEMs were identified, along with potential biomarkers of clinical relevance. Among the altered pathways, alanine, aspartate and glutamate metabolism may play an important role in the development of DOR, providing new directions for further investigation into its molecular mechanisms.</p>

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Molecular characteristics of follicular fluid in advanced maternal age women with different ovarian reserves: a multi-omics study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月12日

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  • Wenlong Qi,
  • Zhicheng Jia,
  • Mengyu Shi,
  • Xinxin Yang,
  • Xinwei Sun,
  • Yongqian Li,
  • Peixuan Wang,
  • Ying Guo

摘要

Background

Age-related diminished ovarian reserve (DOR) exhibits marked significant individual variation. Some women of advanced age with normal ovarian reserve (NOR) achieve better reproductive outcomes than age-matched DOR patients.

Objective

This study aimed to compare the metabolomic and proteomic profiles of follicular fluid (FF) from advanced maternal age(AMA) women with DOR and NOR, to reveal differences in the follicular microenvironment and identify potential biomarkers and related pathways.

Methods

LC-MS/MS was employed to profile metabolites and proteins in FF samples from both groups. Differentially expressed metabolites (DEMs) and differentially expressed proteins (DEPs) were identified using multivariate and univariate statistical analyses. Functional annotation and pathway enrichment analyses were performed using the GO and KEGG databases. Metabolomic and proteomic data were analyzed using bioinformatic approaches to identify key molecules and potential biomarkers associated with DOR.

Results

Untargeted metabolomic analysis identified a total of 89 DEMs, including 32 upregulated and 57 downregulated. Data-independent acquisition (DIA) quantitative proteomic analysis identified 335 DEPs, of which 40 were up-regulated and 295 were down-regulated. Multi-omics analysis revealed significant alterations in several pathways in DOR patients, including metabolic pathways, cholesterol metabolism, alanine, aspartate and glutamate metabolism, carbon metabolism, central carbon metabolism in cancer, and sulfur metabolism. Based on protein expression profiles associated with these dysregulated pathways, four candidate protein biomarkers were further identified.

Conclusions

Based on proteomic and metabolomic analyses, this study systematically characterized the follicular microenvironment of AMA with different ovarian reserve. A series of key DEPs and DEMs were identified, along with potential biomarkers of clinical relevance. Among the altered pathways, alanine, aspartate and glutamate metabolism may play an important role in the development of DOR, providing new directions for further investigation into its molecular mechanisms.