{"title":"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","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":"{\"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}","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}
Integrated mRNA-seq and miRNA-seq analysis reveals miR-210a-5p regulates uterine aging in laying hens by targeting the RASL11B/Raf/MAPK pathway
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.
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.