Cross-species analysis of follicular extracellular vesicle miRNAs revealed conserved regulatory networks in mammalian reproduction

IF 2.9 2区农林科学 Q3 REPRODUCTIVE BIOLOGY

Theriogenology Pub Date : 2026-05-01 Epub Date: 2026-02-05 DOI:10.1016/j.theriogenology.2026.117850

Kaj Chokeshaiusaha , Thanida Sananmuang , Roongtham Kedkovid

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引用次数: 0

Abstract

Extracellular vesicle (EV)-associated microRNAs (miRNAs) mediate intercellular communication within the ovarian follicle, influencing granulosa cell function, oocyte maturation, and follicular development. Despite their biological importance, the evolutionary conservation and divergence of follicular EV-associated miRNA networks across mammalian species remain poorly understood. Here, we presented the novel cross-species comparative analysis of follicular EV miRNAs and their predicted gene regulatory networks across four mammals—human, cow, pig, and horse. Publicly available miRNA-sequencing (miRNA-seq) datasets were reanalyzed using a standardized pipeline integrating miRDeep2 for miRNA detection, TargetScan for conserved target prediction in humans, and IntaRNA for hybridization-based target identification in non-human species.

Detectable miRNAs were identified in human (1,584), cow (679), pig (351), and horse (336). Crucially, only 16 of these miRNAs were shared by all four species. Despite this limited overlap, conserved hub genes—defined as genes targeted by multiple miRNAs—revealed strong functional convergence in pathways regulating RNA metabolism, transcription, and macromolecule biosynthesis. Approximately 1000 hub genes per species were normalized to ensure unbiased comparison, yielding 313 conserved hub genes targeted by shared miRNAs. These genes represented evolutionarily stable regulatory nodes by miRNA essential for follicular communication and oocyte competence.

Although miRNA genomic sequences are highly conserved, their expression and EV-mediated export exhibited species-specific variation, suggesting adaptive regulation aligned with reproductive physiology. Collectively, this study uncovered a deeply conserved post-transcriptional framework that underlaid mammalian follicular function while highlighting species-specific divergence in miRNA deployment. These findings established a molecular foundation for comparative and translational reproductive research across human and veterinary systems.

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卵泡细胞外囊泡mirna的跨物种分析揭示了哺乳动物生殖中保守的调控网络。

细胞外囊泡（EV）相关的microRNAs （miRNAs）介导卵巢卵泡内的细胞间通讯，影响颗粒细胞功能、卵母细胞成熟和卵泡发育。尽管它们具有重要的生物学意义，但哺乳动物物种中卵泡ev相关miRNA网络的进化保护和分化仍然知之甚少。在这里，我们提出了一种新的跨物种比较分析，在四种哺乳动物（人类、牛、猪和马）中，卵泡EV mirna及其预测的基因调控网络。使用标准化管道重新分析公开可用的miRNA测序（miRNA-seq）数据集，整合miRDeep2用于miRNA检测，TargetScan用于人类保守靶标预测，IntaRNA用于非人类物种基于杂交的靶标鉴定。在人（1,584）、牛（679）、猪（351）和马（336）中鉴定出可检测的mirna。至关重要的是，这些mirna中只有16个是所有四个物种共有的。尽管存在这种有限的重叠，但保守的枢纽基因（定义为多个mirna靶向的基因）在调节RNA代谢、转录和大分子生物合成的途径中显示出强大的功能趋同。为了确保无偏比较，每个物种大约有1000个中心基因被归一化，得到313个共享mirna靶向的保守中心基因。这些基因通过对卵泡通讯和卵母细胞能力至关重要的miRNA代表了进化稳定的调控节点。尽管miRNA基因组序列高度保守，但其表达和ev介导的输出表现出物种特异性变异，表明适应性调节与生殖生理一致。总的来说，这项研究揭示了一个深度保守的转录后框架，该框架奠定了哺乳动物滤泡功能，同时强调了miRNA部署的物种特异性差异。这些发现为跨人类和兽医系统的比较和转化生殖研究奠定了分子基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Theriogenology 农林科学-生殖生物学

CiteScore

5.50

自引率

14.30%

发文量

387

审稿时长

72 days

期刊介绍： Theriogenology provides an international forum for researchers, clinicians, and industry professionals in animal reproductive biology. This acclaimed journal publishes articles on a wide range of topics in reproductive and developmental biology, of domestic mammal, avian, and aquatic species as well as wild species which are the object of veterinary care in research or conservation programs.