Differential expression of bovine milk-derived exosomal miRNAs and their role in modulating endometrial receptivity during early pregnancy

IF 2.2 3区农林科学 Q1 VETERINARY SCIENCES

Research in veterinary science Pub Date : 2025-04-14 DOI:10.1016/j.rvsc.2025.105636

Qi Zhu, Jiaxing Guo, Ilyas Alee, Cheng Wang, Lian Li

{"title":"Differential expression of bovine milk-derived exosomal miRNAs and their role in modulating endometrial receptivity during early pregnancy","authors":"Qi Zhu, Jiaxing Guo, Ilyas Alee, Cheng Wang, Lian Li","doi":"10.1016/j.rvsc.2025.105636","DOIUrl":null,"url":null,"abstract":"<div><div>Endometrial receptivity is critical for successful implantation of bovine embryos. MicroRNA (miRNA), as a key regulator of uterine receptivity, is involved in physiological processes such as cell differentiation, proliferation, and apoptosis. The aim of this study was to identify pregnancy-specific miRNAs derived from milk exosomes of non-pregnant and early pregnant cows. In addition, bioinformatics analysis was used to assess the differential expression, target genes, and functions of these miRNAs in order to examine their significance in endometrial cell regulation. Exosomes were isolated from milk using an exosome extraction kit and then identified by Western blotting and transmission electron microscopy. We used Illumina high-throughput sequencing to profile miRNAs and identify differentially expressed miRNAs in bovine milk-derived exosomes at different stages of pregnancy (days 15, 25 and 30) and in non-pregnant cows (day 0). The sequencing data revealed a significant upregulation of bta-miR-125b in pregnant cows at days 15 and 25 compared to non-pregnant cows. Bta-miR-125b targets the Leukemia inhibitory factor (LIF), which is thought to play a critical role in the development of endometrial receptivity by regulating gene expression. KEGG pathway enrichment and Gene Ontology analysis indicated that the target genes of the differential miRNAs were significantly enriched in the key signaling pathways, including the MAPK, phosphatidylinositol signaling system and PI3K-Akt signaling pathways, as well as physiological activities such as RNA polymerase II transcriptional regulation, protein phosphorylation, apoptosis control and cell proliferation regulation. These signaling pathways and physiological activities are all indispensable parts during the process of pregnancy. These findings emphasize bta-miR-125b critical function in regulating endometrial receptivity via important signaling pathways, providing potential indicators for early pregnancy detection and insights into enhancing reproductive efficiency in dairy cows.</div></div>","PeriodicalId":21083,"journal":{"name":"Research in veterinary science","volume":"190 ","pages":"Article 105636"},"PeriodicalIF":2.2000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research in veterinary science","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0034528825001109","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Endometrial receptivity is critical for successful implantation of bovine embryos. MicroRNA (miRNA), as a key regulator of uterine receptivity, is involved in physiological processes such as cell differentiation, proliferation, and apoptosis. The aim of this study was to identify pregnancy-specific miRNAs derived from milk exosomes of non-pregnant and early pregnant cows. In addition, bioinformatics analysis was used to assess the differential expression, target genes, and functions of these miRNAs in order to examine their significance in endometrial cell regulation. Exosomes were isolated from milk using an exosome extraction kit and then identified by Western blotting and transmission electron microscopy. We used Illumina high-throughput sequencing to profile miRNAs and identify differentially expressed miRNAs in bovine milk-derived exosomes at different stages of pregnancy (days 15, 25 and 30) and in non-pregnant cows (day 0). The sequencing data revealed a significant upregulation of bta-miR-125b in pregnant cows at days 15 and 25 compared to non-pregnant cows. Bta-miR-125b targets the Leukemia inhibitory factor (LIF), which is thought to play a critical role in the development of endometrial receptivity by regulating gene expression. KEGG pathway enrichment and Gene Ontology analysis indicated that the target genes of the differential miRNAs were significantly enriched in the key signaling pathways, including the MAPK, phosphatidylinositol signaling system and PI3K-Akt signaling pathways, as well as physiological activities such as RNA polymerase II transcriptional regulation, protein phosphorylation, apoptosis control and cell proliferation regulation. These signaling pathways and physiological activities are all indispensable parts during the process of pregnancy. These findings emphasize bta-miR-125b critical function in regulating endometrial receptivity via important signaling pathways, providing potential indicators for early pregnancy detection and insights into enhancing reproductive efficiency in dairy cows.

查看原文本刊更多论文

子宫内膜容受性是牛胚胎成功着床的关键。微RNA（miRNA）是子宫接受性的关键调节因子，参与细胞分化、增殖和凋亡等生理过程。本研究的目的是从非妊娠和早期妊娠奶牛的乳汁外泌体中鉴定妊娠特异性 miRNA。此外，还利用生物信息学分析评估这些 miRNA 的差异表达、靶基因和功能，以研究它们在子宫内膜细胞调控中的意义。我们使用外泌体提取试剂盒从牛奶中分离出外泌体，然后用 Western 印迹法和透射电子显微镜进行鉴定。我们利用Illumina高通量测序技术分析了miRNAs，并鉴定了不同妊娠阶段（第15、25和30天）和非妊娠奶牛（第0天）牛奶外泌体中不同表达的miRNAs。测序数据显示，与非怀孕奶牛相比，怀孕奶牛在第15天和第25天的bta-miR-125b明显上调。Bta-miR-125b靶向白血病抑制因子（LIF），该因子被认为通过调节基因表达在子宫内膜接受性的发育过程中发挥关键作用。KEGG 通路富集和基因本体分析表明，差异 miRNA 的靶基因显著富集于关键信号通路，包括 MAPK、磷脂酰肌醇信号系统和 PI3K-Akt 信号通路，以及 RNA 聚合酶 II 转录调控、蛋白磷酸化、细胞凋亡调控和细胞增殖调控等生理活动。这些信号通路和生理活动都是妊娠过程中不可或缺的部分。这些发现强调了 bta-miR-125b 在通过重要信号通路调节子宫内膜接受性方面的关键功能，为早期妊娠检测提供了潜在指标，并为提高奶牛繁殖效率提供了启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Research in veterinary science 农林科学-兽医学

CiteScore

4.40

自引率

4.20%

发文量

312

审稿时长

75 days

期刊介绍： Research in Veterinary Science is an International multi-disciplinary journal publishing original articles, reviews and short communications of a high scientific and ethical standard in all aspects of veterinary and biomedical research. The primary aim of the journal is to inform veterinary and biomedical scientists of significant advances in veterinary and related research through prompt publication and dissemination. Secondly, the journal aims to provide a general multi-disciplinary forum for discussion and debate of news and issues concerning veterinary science. Thirdly, to promote the dissemination of knowledge to a broader range of professions, globally. High quality papers on all species of animals are considered, particularly those considered to be of high scientific importance and originality, and with interdisciplinary interest. The journal encourages papers providing results that have clear implications for understanding disease pathogenesis and for the development of control measures or treatments, as well as those dealing with a comparative biomedical approach, which represents a substantial improvement to animal and human health. Studies without a robust scientific hypothesis or that are preliminary, or of weak originality, as well as negative results, are not appropriate for the journal. Furthermore, observational approaches, case studies or field reports lacking an advancement in general knowledge do not fall within the scope of the journal.