He Haorong, Yu Xinghong, Cui Can, Zhang Yao, Li Zhuanjian, Han Shunshun, Yin Huadong
Laboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
Poult Sci. 2025 May 17;104(8):105313. doi: 10.1016/j.psj.2025.105313.
The reproductive performance of hens is predominantly determined by the growth and development of their follicles. Follicular development in chickens represents a highly complex and multi-regulatory biological process, wherein granulosa cells (GCs) play a crucial role in follicle selection. Recent studies have emphasized the critical role of circular RNAs (circRNAs) in regulating follicular growth and development in animals. In our previous study, employing circRNA RNA-seq, we identified differential expression of circRALGPS2 between healthy and atretic follicles in chickens. In the current investigation, we observed a marked increase in autophagy and apoptosis levels within atretic follicles. Notably, circRALGPS2 was shown to promote follicular atresia by enhancing autophagy and apoptosis in GCs. Moreover, we demonstrated that circRALGPS2 functions as a molecular sponge for miR-200a-3p, revealing that miR-200a-3p and circRALGPS2 exert antagonistic effects on GC autophagy and apoptosis. Mechanistically, circRALGPS2 targets miR-200a-3p, which subsequently modulates the expression of transforming growth factor β2 (TGFβ2), thereby activating the canonical TGFβ/SMAD signaling pathway. Collectively, our findings demonstrate that circRALGPS2 promotes apoptosis and autophagy in chicken GCs through activation of the TGFβ2/SMAD pathway via miR-200a-3p sequestration. These results provide valuable insights for advancing chicken genetic breeding technologies through marker-assisted selection.
母鸡的繁殖性能主要由其卵泡的生长和发育决定。鸡的卵泡发育是一个高度复杂且受多种调节的生物学过程，其中颗粒细胞（GCs）在卵泡选择中起关键作用。最近的研究强调了环状RNA（circRNAs）在调节动物卵泡生长和发育中的关键作用。在我们之前的研究中，通过circRNA RNA测序，我们鉴定了鸡健康卵泡和闭锁卵泡之间circRALGPS2的差异表达。在当前的研究中，我们观察到闭锁卵泡内自噬和凋亡水平显著增加。值得注意的是，circRALGPS2被证明通过增强颗粒细胞中的自噬和凋亡来促进卵泡闭锁。此外，我们证明circRALGPS2作为miR-200a-3p的分子海绵，揭示了miR-200a-3p和circRALGPS2对颗粒细胞自噬和凋亡发挥拮抗作用。机制上，circRALGPS2靶向miR-200a-3p，miR-200a-3p随后调节转化生长因子β2（TGFβ2）的表达，从而激活经典的TGFβ/SMAD信号通路。总的来说，我们的研究结果表明，circRALGPS2通过miR-200a-3p的隔离激活TGFβ2/SMAD通路，从而促进鸡颗粒细胞的凋亡和自噬。这些结果为通过标记辅助选择推进鸡遗传育种技术提供了有价值的见解。
