Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS

Abstract Background Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder in women of reproductive age. The granulosa cell metabolism correlated with oocyte competence. However, the alteration of fatty acid in granulosa cell of PCOS patients is unclear. Besides, obesity...

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Main Authors: Ye Tian, Aiyuan Wang, Fang Li, Siyu Wang, Jie Shang, Kai Zhang, Xiaohong Bai
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Ovarian Research
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Online Access:https://doi.org/10.1186/s13048-025-01711-5
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author Ye Tian
Aiyuan Wang
Fang Li
Siyu Wang
Jie Shang
Kai Zhang
Xiaohong Bai
author_facet Ye Tian
Aiyuan Wang
Fang Li
Siyu Wang
Jie Shang
Kai Zhang
Xiaohong Bai
author_sort Ye Tian
collection DOAJ
description Abstract Background Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder in women of reproductive age. The granulosa cell metabolism correlated with oocyte competence. However, the alteration of fatty acid in granulosa cell of PCOS patients is unclear. Besides, obesity per se is related to dysfunction of oocyte quality. Hence, this study was aimed to comprehensively investigate the fatty acid alteration of oocyte environment and their associations with embryo quality in normal weight women with PCOS. Method Two independent prospective cohorts included women with PCOS and age-BMI-matched controls that underwent IVF treatment were recruited. DIA-mass spectrometry-based proteomics analysis and absolute quantification of fatty acids were conducted in granulosa cells and follicular fluid from women with PCOS and controls, and then the relationship between fatty acid level and embryo quality in PCOS patients was analysed. Results Proteomic analysis in cohort 1 revealed 205 differentially expressed proteins in the granulosa cells of normal-weight PCOS patients compared with those of controls. Functional enrichment analysis and metabolism score calculation revealed that fatty acid metabolism pathways, especially the biosynthesis of unsaturated fatty acids, were downregulated. The hallmark fatty acid metabolism score was negatively correlated with the total testosterone level and the AMH level (R=-0.52, P = 0.004; R=-0.64, P = 0.00017, respectively).Compared with those in the control group, the levels of the SFAs myristic acid (C14:0) and MUFAs nervonic acid (C24:1) in the follicular fluid of PCOS patients in cohort 1 were greater, whereas the ratio of PUFAs LA: ALA was lower, which were validated by cohort 2. C14:0 was moderately positively correlated with the basal LH level and LH/FSH ratio, even after correction for multiple comparisons. Receiver operating characteristic (ROC) analysis combining the C24:1, C14:0, and LA: ALA ratios with the seven fatty acid metabolic-related proteins revealed that the predictive accuracy for PCOS was 0.86. Conclusion In normal-weight women with PCOS, fatty acid disturbance occurs in granulosa cells and follicular fluid, and also suggesting a role for C14:0, C24:1 and LA: ALA in PCOS patients, independent of obesity.
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spelling doaj-art-69f9242af13e4e4abc7d5bb65ff73b3d2025-08-20T02:07:41ZengBMCJournal of Ovarian Research1757-22152025-06-0118111410.1186/s13048-025-01711-5Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOSYe Tian0Aiyuan Wang1Fang Li2Siyu Wang3Jie Shang4Kai Zhang5Xiaohong Bai6Department of Gynecology and Obstetrics, Tianjin Medical University General HospitalThe Province and Ministry Cosponsored, Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Gynecology and Obstetrics, Tianjin Medical University General HospitalThe Province and Ministry Cosponsored, Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Gynecology and Obstetrics, Tianjin Medical University General HospitalThe Province and Ministry Cosponsored, Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Gynecology and Obstetrics, Tianjin Medical University General HospitalAbstract Background Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder in women of reproductive age. The granulosa cell metabolism correlated with oocyte competence. However, the alteration of fatty acid in granulosa cell of PCOS patients is unclear. Besides, obesity per se is related to dysfunction of oocyte quality. Hence, this study was aimed to comprehensively investigate the fatty acid alteration of oocyte environment and their associations with embryo quality in normal weight women with PCOS. Method Two independent prospective cohorts included women with PCOS and age-BMI-matched controls that underwent IVF treatment were recruited. DIA-mass spectrometry-based proteomics analysis and absolute quantification of fatty acids were conducted in granulosa cells and follicular fluid from women with PCOS and controls, and then the relationship between fatty acid level and embryo quality in PCOS patients was analysed. Results Proteomic analysis in cohort 1 revealed 205 differentially expressed proteins in the granulosa cells of normal-weight PCOS patients compared with those of controls. Functional enrichment analysis and metabolism score calculation revealed that fatty acid metabolism pathways, especially the biosynthesis of unsaturated fatty acids, were downregulated. The hallmark fatty acid metabolism score was negatively correlated with the total testosterone level and the AMH level (R=-0.52, P = 0.004; R=-0.64, P = 0.00017, respectively).Compared with those in the control group, the levels of the SFAs myristic acid (C14:0) and MUFAs nervonic acid (C24:1) in the follicular fluid of PCOS patients in cohort 1 were greater, whereas the ratio of PUFAs LA: ALA was lower, which were validated by cohort 2. C14:0 was moderately positively correlated with the basal LH level and LH/FSH ratio, even after correction for multiple comparisons. Receiver operating characteristic (ROC) analysis combining the C24:1, C14:0, and LA: ALA ratios with the seven fatty acid metabolic-related proteins revealed that the predictive accuracy for PCOS was 0.86. Conclusion In normal-weight women with PCOS, fatty acid disturbance occurs in granulosa cells and follicular fluid, and also suggesting a role for C14:0, C24:1 and LA: ALA in PCOS patients, independent of obesity.https://doi.org/10.1186/s13048-025-01711-5PCOSFatty acidGranulosa cellProteomics
spellingShingle Ye Tian
Aiyuan Wang
Fang Li
Siyu Wang
Jie Shang
Kai Zhang
Xiaohong Bai
Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS
Journal of Ovarian Research
PCOS
Fatty acid
Granulosa cell
Proteomics
title Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS
title_full Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS
title_fullStr Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS
title_full_unstemmed Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS
title_short Fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal-weight women with PCOS
title_sort fatty acid metabolism of granulose cells and follicular fluid and their associations with embryo quality in normal weight women with pcos
topic PCOS
Fatty acid
Granulosa cell
Proteomics
url https://doi.org/10.1186/s13048-025-01711-5
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