Background 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 poo...Background 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.Results 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.Conclusions 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.展开更多
目的进一步探讨缺氧后血管新生的调控机制。方法常规方法培养人微血管内皮细胞,低氧培养箱制备内皮细胞缺氧模型(观察组),正常细胞作为对照组。采用real time PCR法检测两组内皮特异性microRNA(miR-210、miR-92a、miR-126)表达变化。结...目的进一步探讨缺氧后血管新生的调控机制。方法常规方法培养人微血管内皮细胞,低氧培养箱制备内皮细胞缺氧模型(观察组),正常细胞作为对照组。采用real time PCR法检测两组内皮特异性microRNA(miR-210、miR-92a、miR-126)表达变化。结果与对照组比较,miR-210、miR-92a、miR-126分别上调了(5.19±0.99)、(3.02±0.88)、(3.87±0.83)倍,P均<0.05。结论缺氧可促使内皮细胞特异性microRNA表达改变,此可能为缺氧后血管新生的主要调控机制。展开更多
基金funded by the National Key Research and Development Program of China,grant number 2021YFD1300600Sichuan Science and Technology Program(2024YFNH0025,2022YFYZ0005,2021YFYZ0031)China Agriculture Research System of MOF and MARA(CARS-40).
文摘Background 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.Results 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.Conclusions 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.
基金support by the National Natural Science Foundation of China(No.31372398)Ph.D.Programs Foundation of Ministry of Education of China(No.20132305110004)+1 种基金the Natural Science Foundation of Heilongjiang Province of China(No.C2015041)Open Project of the Key Laboratory Subject of Heilongjiang Provincial Department of Education of China(No.AMKL201302)
文摘目的进一步探讨缺氧后血管新生的调控机制。方法常规方法培养人微血管内皮细胞,低氧培养箱制备内皮细胞缺氧模型(观察组),正常细胞作为对照组。采用real time PCR法检测两组内皮特异性microRNA(miR-210、miR-92a、miR-126)表达变化。结果与对照组比较,miR-210、miR-92a、miR-126分别上调了(5.19±0.99)、(3.02±0.88)、(3.87±0.83)倍,P均<0.05。结论缺氧可促使内皮细胞特异性microRNA表达改变,此可能为缺氧后血管新生的主要调控机制。
