Abstract
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.
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Details
1 Sichuan Agricultural University, State Key Laboratory of Swine and Poultry Breeding Industry, Key Laboratory of Agricultural Bioinformatics, Ministry of Education, Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, and, Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan, People’s Republic of China (GRID:grid.80510.3c) (ISNI:0000 0001 0185 3134)
2 China Agricultural University, State Key Laboratory of Animal Biotech Breeding, Frontier Science Center of Molecular Design Breeding, Beijing, China (GRID:grid.22935.3f) (ISNI:0000 0004 0530 8290)