Exploration of the mechanism of PCOS induced by microenvironmental changes in follicular fluid based on 16 S rRNA and metabolomics.

IF 4.2 3区医学 Q1 REPRODUCTIVE BIOLOGY

Journal of Ovarian Research Pub Date : 2025-09-24 DOI:10.1186/s13048-025-01781-5

Cong Wang, Huimin Zhao, Andriy Sibirny, Weihua Pan, Rubing Liang, Gang Luo, Gongyou Zhang, Yanyan Wang, Yingqian Kang

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引用次数: 0

Abstract

Background: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of childbearing age. The follicular microenvironment plays a vital role in oocyte development as one of the important factors affecting PCOS. This study aimed to reveal the changes in the follicular microenvironment of PCOS rats using multi-omics analysis.

Methods: A PCOS rat model was constructed using dehydroepiandrosterone (DHEA) method, and 16 S rRNA amplicon sequencing and non-targeted metabolomics were applied to analyze the follicular fluid samples from the control and the PCOS groups. The key microbiota were screened using T-test analysis, and the key metabolites were identified through Spearman correlation hierarchical cluster analysis. Bioinformatics and network pharmacology were used to identify overlapping genes between the key metabolite targets and PCOS-related targets, followed by Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.

Results: There were significant differences in the microbiome composition between the two groups, with a general decrease in the microbial abundance in the follicular fluid of the PCOS group compared to the control group. T-test analysis identified Acinetobacter haemolyticus as a significantly different strain. Spearman correlation analysis exhibited a positive correlation between Acinetobacter haemolyticus and three metabolites (S-adenosylmethioninamine, prorocentrolide, and cilostazol). Network pharmacology and bioinformatics analyses revealed that the overlapping genes of these metabolites targets and PCOS-related targets were enriched in autophagy-related signaling pathways, with cilostazol as a candidate metabolite and SRC as a potential target. Additionally, Liquid Chromatography-Mass Spectrometry (LC-MS) analysis confirmed the presence of Acinetobacter haemolyticus in the follicular fluid of rats and its ability to metabolize cilostazol.

Conclusions: Cilostazol is a significantly differentiated metabolite in the follicular microenvironment of PCOS rats, playing a role in PCOS development by regulating autophagy-related signaling processes mediated by SRC.

Clinical trial number: Not applicable.

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基于16s rRNA和代谢组学的卵泡液微环境变化致多囊卵巢综合征机制探讨

背景：多囊卵巢综合征（PCOS）是育龄妇女常见的生殖内分泌疾病。卵泡微环境在卵母细胞发育中起着至关重要的作用，是影响PCOS的重要因素之一。本研究旨在通过多组学分析揭示多囊卵巢综合征大鼠卵泡微环境的变化。方法：采用脱氢表雄酮（DHEA）法建立PCOS大鼠模型，采用16s rRNA扩增子测序和非靶向代谢组学方法对对照组和PCOS组卵泡液样本进行分析。采用t检验分析筛选关键菌群，采用Spearman相关分层聚类分析鉴定关键代谢物。利用生物信息学和网络药理学方法鉴定关键代谢物靶点与pcos相关靶点之间的重叠基因，然后进行基因本体（GO）分类和京都基因与基因组百科全书（KEGG）途径富集分析。结果：两组之间的微生物组组成存在显著差异，PCOS组卵泡液中微生物丰度与对照组相比普遍降低。t检验分析鉴定溶血不动杆菌为显著不同的菌株。Spearman相关分析显示溶血不动杆菌与3种代谢物（s -腺苷蛋氨酸胺、原心特罗利特和西洛他唑）呈正相关。网络药理学和生物信息学分析显示，这些代谢物靶点和pcos相关靶点的重叠基因在自噬相关信号通路中富集，西洛他唑是候选代谢物，SRC是潜在靶点。此外，液相色谱-质谱（LC-MS）分析证实了大鼠卵泡液中溶血不动杆菌的存在及其代谢西洛他唑的能力。结论：西洛他唑是PCOS大鼠滤泡微环境中显著分化的代谢物，通过调节SRC介导的自噬相关信号过程，参与PCOS的发生发展。临床试验号：不适用。

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来源期刊

Journal of Ovarian Research REPRODUCTIVE BIOLOGY-

CiteScore

6.20

自引率

2.50%

发文量

125

审稿时长

>12 weeks

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.