Lin Zhongzhen, Gong Yanrong, Yu Chunlin, Yang Chaowu, Yin Lingqian, Zhang Donghao, Tang Yuan, Xu Feng, Wang Ye, Liu Yiping
State Key Laboratory of Swine and Poultry Breeding Industry, 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 Agricultural University, Chengdu, China.
Animal Breeding and Genetics Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Chengdu, China.
Poult Sci. 2025 Feb;104(2):104761. doi: 10.1016/j.psj.2024.104761. Epub 2024 Dec 31.
For commercial laying hens, the continuous high-intensity ovulation process leads to a significant accumulation of reactive oxygen species (ROS) in the granulosa cells, inducing oxidative stress, which accelerates ovarian aging and shortens the peak laying period. The molecular mechanisms underlying this process remain poorly understood. Therefore, we modeled the processes of oxidative stress and antioxidant in chicken granulosa cells. Small RNA sequencing revealed that miR-15c-3p expression was elevated by oxidative stress induction and attenuated by antioxidant curcumin. Functional validation with miR-15c-3p mimic and inhibitor confirmed the role of miR-15c-3p in exacerbating oxidative stress and resultant suppression of lipid droplet storage and progesterone secretion in chicken granulosa cells by targeting insulin-like growth factor 2 binding protein 3 (IGF2BP3). These regulatory effects were mediated through the sequential downstream signaling cascade of AKT-Raf1-ERK1/2. In conclusion, IGF2BP3 curbed by miR-15c-3p restores disrupted lipid storage and progesterone secretion in chicken granulosa cells under oxidative stress through AKT-Raf1-ERK1/2 signaling pathway. These findings offer new insights into the molecular mechanisms by which oxidative stress damages reproductive capacity and a theoretical basis for mitigating oxidative stress in laying hens through genetic improvement.
对于商业产蛋母鸡而言，持续的高强度排卵过程会导致颗粒细胞中活性氧（ROS）大量积累，引发氧化应激，进而加速卵巢衰老并缩短产蛋高峰期。该过程背后的分子机制仍知之甚少。因此，我们对鸡颗粒细胞中的氧化应激和抗氧化过程进行了建模。小RNA测序显示，氧化应激诱导可使miR-15c-3p表达升高，而抗氧化剂姜黄素则使其表达减弱。使用miR-15c-3p模拟物和抑制剂进行的功能验证证实，miR-15c-3p通过靶向胰岛素样生长因子2结合蛋白3（IGF2BP3），在加剧鸡颗粒细胞氧化应激以及由此导致的脂质滴储存和孕酮分泌抑制中发挥作用。这些调节作用是通过AKT-Raf1-ERK1/2的下游信号级联顺序介导的。总之，在氧化应激下，受miR-15c-3p抑制的IGF2BP3通过AKT-Raf1-ERK1/2信号通路恢复鸡颗粒细胞中受损的脂质储存和孕酮分泌。这些发现为氧化应激损害生殖能力的分子机制提供了新见解，并为通过基因改良减轻产蛋母鸡氧化应激提供了理论依据。
