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奶牛卵巢滤泡囊肿中的调控RNA网络:对人类多囊卵巢综合征的启示

Regulatory RNA Networks in Ovarian Follicular Cysts in Dairy Cows: Implications for Human Polycystic Ovary Syndrome.

作者信息

Kasimanickam Ramanathan, Kasimanickam Vanmathy, Ferreira Joao, Kastelic John, de Souza Fabiana

机构信息

College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.

School of Veterinary Medicine and Animal Science, São Paulo State University-UNESP, Botucatu 18618-681, São Paulo, Brazil.

出版信息

Genes (Basel). 2025 Jun 30;16(7):791. doi: 10.3390/genes16070791.

Abstract

: Ovarian follicular cysts (OFCs) in dairy cows represent a significant cause of infertility and share striking similarities with polycystic ovary syndrome (PCOS) in women. This study aimed to elucidate the molecular mechanisms underlying OFCs and their relevance to PCOS by profiling differentially expressed (DE) microRNAs (miRNAs) and constructing integrative RNA interaction networks. : Expression analysis of 84 bovine miRNAs was conducted in antral follicular fluid from normal and cystic follicles using miScript PCR arrays. Bioinformatic tools including miRBase, miRNet, and STRING were employed to predict miRNA targets, construct protein-protein interaction networks, and perform gene ontology and KEGG pathway enrichment. Network analyses integrated miRNAs with coding (mRNAs) and non-coding RNAs (circRNAs, lncRNAs, snRNAs). : Seventeen miRNAs were significantly dysregulated in OFCs, including bta-miR-18a, bta-miR-30e-5p, and bta-miR-15b-5p, which were associated with follicular arrest, insulin resistance, and impaired steroidogenesis. Upregulated miRNAs such as bta-miR-132 and bta-miR-145 correlated with inflammation, oxidative stress, and intrafollicular androgen excess. Key regulatory lncRNAs such as Nuclear Enriched Abundant Transcript 1 (NEAT1), Potassium Voltage-Gated Channel Subfamily Q Member 1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1), Taurine-Upregulated 1 (TUG1), and X Inactive Specific Transcript (XIST), as well as circRNA/pseudogene hubs, were identified, targeting pathways involved in metabolism, inflammation, steroidogenesis, cell cycle, and apoptosis. : The observed transcriptomic changes mirror core features of human PCOS, supporting the use of bovine OFCs as a comparative model. These findings provide novel insights into the regulatory RNA networks driving ovarian dysfunction and suggest potential biomarkers and therapeutic targets for reproductive disorders. This network-based approach enhances our understanding of the complex transcriptomic landscape associated with follicular pathologies in both cattle and women.

摘要

奶牛的卵巢滤泡囊肿(OFCs)是导致不孕的一个重要原因,且与女性的多囊卵巢综合征(PCOS)有着显著的相似之处。本研究旨在通过分析差异表达(DE)的微小RNA(miRNA)并构建整合的RNA相互作用网络,阐明OFCs潜在的分子机制及其与PCOS的相关性。

使用miScript PCR阵列对来自正常卵泡和囊肿卵泡的窦状卵泡液中的84种牛miRNA进行表达分析。利用包括miRBase、miRNet和STRING在内的生物信息学工具预测miRNA靶标、构建蛋白质-蛋白质相互作用网络,并进行基因本体论和KEGG通路富集分析。网络分析将miRNA与编码(mRNA)和非编码RNA(circRNA、lncRNA、snRNA)整合在一起。

17种miRNA在OFCs中显著失调,包括bta-miR-18a、bta-miR-30e-5p和bta-miR-15b-5p,它们与卵泡停滞、胰岛素抵抗和类固醇生成受损有关。上调的miRNA如bta-miR-132和bta-miR-145与炎症、氧化应激和卵泡内雄激素过量相关。鉴定出关键的调控lncRNA,如核富集丰富转录本1(NEAT1)、钾电压门控通道亚家族Q成员1反义链/反义转录本1(KCNQ1OT1)、牛磺酸上调基因1(TUG1)和X染色体失活特异性转录本(XIST),以及circRNA/假基因枢纽,它们靶向参与代谢、炎症、类固醇生成、细胞周期和凋亡的通路。

观察到的转录组变化反映了人类PCOS的核心特征,支持将牛OFCs作为一种比较模型。这些发现为驱动卵巢功能障碍的调控RNA网络提供了新的见解,并为生殖障碍提出了潜在的生物标志物和治疗靶点。这种基于网络的方法增强了我们对与牛和女性卵泡病变相关的复杂转录组格局的理解。

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