Zhou Qijun, Geng Zijian, Lian Shuai, Wang Jianfa, Wu Rui
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Daqing 163319, China.
China Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing 163319, China.
Animals (Basel). 2025 May 14;15(10):1419. doi: 10.3390/ani15101419.
Mammary glands in cows are highly dynamic, making genomic stability particularly crucial. Continuous lactation and self-renewal of these glands are primary contributors to genomic instability. We employed transcriptomic and proteomic methods to analyze the expressional characteristics in the mammary glands of cows with varying levels of milk production. Our findings indicated differences in relevant pathways, including DNA damage repair and apoptosis, which are influenced by increasing parity. Notably, ATR protein levels in the mammary glands of low-yield dairy cows were reduced. Following in vitro silencing of ATR, β-galactosidase content increased in aging mammary epithelial cells, with cell cycle arrest in the G2 and S phases. Secretory phenotypes associated with aging, including IL-6, IL-10, IL-1β, INF-γ, and IL-2, were elevated, along with increased TNF-α content. The expressions of DNA repair-related proteins, including PIG3, PARP1, and Cleaved caspase3, were upregulated, and SP1 expression was decreased. Furthermore, the expressions of cytochrome C and BAK increased, and ATR silencing inhibited mTOR and STAT5 lactation signaling pathways, resulting in elevated STAT3 protein levels associated with mammary gland degeneration. This study emphasizes the significance of the ATR protein in the mammary glands of dairy cows, contributing valuable insights into maintaining their health and presenting a novel perspective on strategies to enhance their lifespan.
奶牛的乳腺具有高度动态性，因此基因组稳定性尤为关键。这些腺体的持续泌乳和自我更新是导致基因组不稳定的主要因素。我们采用转录组学和蛋白质组学方法分析了不同产奶水平奶牛乳腺中的表达特征。我们的研究结果表明，包括DNA损伤修复和细胞凋亡在内的相关途径存在差异，这些差异受胎次增加的影响。值得注意的是，低产奶牛乳腺中ATR蛋白水平降低。在体外沉默ATR后，衰老乳腺上皮细胞中的β-半乳糖苷酶含量增加，细胞周期停滞在G2期和S期。与衰老相关的分泌表型，包括IL-6、IL-10、IL-1β、INF-γ和IL-2升高，同时TNF-α含量增加。包括PIG3、PARP1和裂解的caspase3在内的DNA修复相关蛋白的表达上调，而SP1表达下降。此外，细胞色素C和BAK的表达增加，ATR沉默抑制了mTOR和STAT5泌乳信号通路，导致与乳腺退化相关的STAT3蛋白水平升高。本研究强调了ATR蛋白在奶牛乳腺中的重要性，为维持奶牛健康提供了有价值的见解，并为延长其寿命的策略提供了新的视角。
