Integrated mRNA-seq and miRNA-seq analysis reveals miR-210a-5p regulates uterine aging in laying hens by targeting the RASL11B/Raf/MAPK pathway

IF 6.5 1区 农林科学 Q1 Agricultural and Biological Sciences
Xiyu Zhao, Xinyan Li, Wenxin Zhang, Mingyue Gao, Conghao Zhong, Boxuan Zhang, Congjiao Sun, Yao Zhang, Shunshun Han, Huadong Yin
{"title":"Integrated mRNA-seq and miRNA-seq analysis reveals miR-210a-5p regulates uterine aging in laying hens by targeting the RASL11B/Raf/MAPK pathway","authors":"Xiyu Zhao, Xinyan Li, Wenxin Zhang, Mingyue Gao, Conghao Zhong, Boxuan Zhang, Congjiao Sun, Yao Zhang, Shunshun Han, Huadong Yin","doi":"10.1186/s40104-025-01257-y","DOIUrl":null,"url":null,"abstract":"Uterine aging is a key factor contributing to the deterioration of egg quality and reproductive performance in laying hens. Despite its importance, the molecular mechanisms underlying uterine aging remain poorly defined. This study aimed to characterize gene expression and regulatory changes associated with uterine aging in hens at different life stages. Transcriptomic Analysis of uterine tissue from hens aged 350, 500, And 700 d revealed dynamic changes in gene expression patterns during aging. A significant upregulation of genes involved in cellular senescence was observed, including increased expression of the p53 signaling pathway And markers associated with inflammation And cell cycle arrest. The most notable changes occurred between 350 And 500 d of age, suggesting this as a critical window for the onset of uterine aging. MicroRNA sequencing identified miR-210a-5p as significantly reduced with age. Target prediction and experimental validation showed that miR-210a-5p directly suppresses the expression of RASL11B, a Ras-like small GTPase that activates the MAPK signaling pathway. In primary uterine epithelial cells, reduced miR-210a-5p levels led to elevated RASL11B expression, increased activation of B-Raf, MEK, and ERK proteins, and enhanced expression of aging-related genes and inflammatory factors. In contrast, overexpression of miR-210a-5p or inhibition of the MAPK pathway delayed senescence and reduced inflammatory signaling. RASL11B overexpression was sufficient to induce aging phenotypes, confirming its central role in promoting uterine cellular aging. This study identifies a novel regulatory pathway in which miR-210a-5p modulates uterine aging through the RASL11B-MAPK signaling cascade. The findings provide mechanistic insight into age-related reproductive decline in hens and suggest that targeting this pathway may offer new strategies for maintaining uterine function and extending reproductive lifespan in poultry.","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"8 1","pages":""},"PeriodicalIF":6.5000,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Animal Science and Biotechnology","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1186/s40104-025-01257-y","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Agricultural and Biological Sciences","Score":null,"Total":0}
引用次数: 0

Abstract

Uterine aging is a key factor contributing to the deterioration of egg quality and reproductive performance in laying hens. Despite its importance, the molecular mechanisms underlying uterine aging remain poorly defined. This study aimed to characterize gene expression and regulatory changes associated with uterine aging in hens at different life stages. Transcriptomic Analysis of uterine tissue from hens aged 350, 500, And 700 d revealed dynamic changes in gene expression patterns during aging. A significant upregulation of genes involved in cellular senescence was observed, including increased expression of the p53 signaling pathway And markers associated with inflammation And cell cycle arrest. The most notable changes occurred between 350 And 500 d of age, suggesting this as a critical window for the onset of uterine aging. MicroRNA sequencing identified miR-210a-5p as significantly reduced with age. Target prediction and experimental validation showed that miR-210a-5p directly suppresses the expression of RASL11B, a Ras-like small GTPase that activates the MAPK signaling pathway. In primary uterine epithelial cells, reduced miR-210a-5p levels led to elevated RASL11B expression, increased activation of B-Raf, MEK, and ERK proteins, and enhanced expression of aging-related genes and inflammatory factors. In contrast, overexpression of miR-210a-5p or inhibition of the MAPK pathway delayed senescence and reduced inflammatory signaling. RASL11B overexpression was sufficient to induce aging phenotypes, confirming its central role in promoting uterine cellular aging. This study identifies a novel regulatory pathway in which miR-210a-5p modulates uterine aging through the RASL11B-MAPK signaling cascade. The findings provide mechanistic insight into age-related reproductive decline in hens and suggest that targeting this pathway may offer new strategies for maintaining uterine function and extending reproductive lifespan in poultry.
综合mRNA-seq和miRNA-seq分析发现,miR-210a-5p通过靶向RASL11B/Raf/MAPK通路调控蛋鸡子宫衰老
子宫老化是导致蛋鸡蛋品质和繁殖性能下降的关键因素。尽管它很重要,但子宫衰老的分子机制仍然不明确。本研究旨在研究不同生命阶段母鸡子宫衰老相关的基因表达和调控变化。对35、500和700 d龄母鸡子宫组织的转录组学分析揭示了衰老过程中基因表达模式的动态变化。研究发现,与细胞衰老有关的基因显著上调,包括p53信号通路和与炎症和细胞周期阻滞相关的标志物的表达增加。最显著的变化发生在350和500天之间,这表明这是子宫衰老开始的关键窗口期。MicroRNA测序发现miR-210a-5p随着年龄的增长而显著降低。靶标预测和实验验证表明,miR-210a-5p直接抑制RASL11B的表达,RASL11B是一种激活MAPK信号通路的ras样小GTPase。在原代子宫上皮细胞中,miR-210a-5p水平降低导致RASL11B表达升高,B-Raf、MEK和ERK蛋白激活增加,衰老相关基因和炎症因子表达增强。相反,过表达miR-210a-5p或抑制MAPK通路会延缓衰老并减少炎症信号。RASL11B过表达足以诱导衰老表型,证实其在促进子宫细胞衰老中的核心作用。本研究确定了miR-210a-5p通过RASL11B-MAPK信号级联调节子宫衰老的新调控途径。这些发现为母鸡年龄相关的生殖能力下降提供了机制见解,并表明针对这一途径可能提供维持子宫功能和延长家禽生殖寿命的新策略。
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
Journal of Animal Science and Biotechnology
Journal of Animal Science and Biotechnology AGRICULTURE, DAIRY & ANIMAL SCIENCE-
CiteScore
9.90
自引率
2.90%
发文量
822
审稿时长
17 weeks
期刊介绍: Journal of Animal Science and Biotechnology is an open access, peer-reviewed journal that encompasses all aspects of animal science and biotechnology. That includes domestic animal production, animal genetics and breeding, animal reproduction and physiology, animal nutrition and biochemistry, feed processing technology and bioevaluation, animal biotechnology, and meat science.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信