State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, 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, China.
Int J Mol Sci. 2024 Aug 21;25(16):9061. doi: 10.3390/ijms25169061.
Follicle development refers to the process in which the follicles in the ovary gradually develop from the primary stage to a mature state, and most primary follicles fail to develop normally, without forming a dense granular cell layer and cell wall, which is identified as atretic follicles. Granulosa cells assist follicle development by producing hormones and providing support, and interference in the interaction between granulosa cells and oocytes may lead to the formation of atretic follicles. Ferroptosis, as a non-apoptotic form of death, is caused by cells accumulating lethal levels of iron-dependent phospholipid peroxides. Healthy follicles ranging from 4 to 5 mm were randomly divided into two groups: a control group (DMSO) and treatment group (10 uM of ferroptosis inducer erastin). Each group was sequenced after three repeated cultures for 24 h. We found that ferroptosis was associated with atretic follicles and that the in vitro treatment of healthy follicles with the ferroptosis inducer erastin produced a phenotype similar to that of atretic follicles. Overall, our study elucidates that tRF-1:30-Gly-GCC-2 is involved in the apoptosis and ferroptosis of GCs. Mechanistically, tRF-1:30-Gly-GCC-2 inhibits granulosa cell proliferation and promotes ferroptosis by inhibiting Mitogen-activated protein kinase 1 (). tRF-1:30-Gly-GCC-2 may be a novel molecular target for improving the development of atretic follicles in ovarian dysfunction. In conclusion, our study provides a new perspective on the pathogenesis of granulosa cell dysfunction and follicular atresia.
卵泡发育是指卵巢中的卵泡逐渐从初级阶段发育到成熟状态的过程，大多数初级卵泡不能正常发育，没有形成密集的颗粒细胞层和细胞壁，被鉴定为闭锁卵泡。颗粒细胞通过产生激素和提供支持来协助卵泡发育，干扰颗粒细胞和卵母细胞之间的相互作用可能导致闭锁卵泡的形成。铁死亡作为一种非凋亡形式的死亡，是由细胞积累致死水平的铁依赖性磷脂过氧化物引起的。从 4 到 5 毫米的健康卵泡被随机分为两组：对照组（DMSO）和治疗组（10 μM 的铁死亡诱导剂 erastin）。每组在重复培养 24 h 后进行三次重复培养。我们发现铁死亡与闭锁卵泡有关，用铁死亡诱导剂 erastin 体外处理健康卵泡会产生类似于闭锁卵泡的表型。总的来说，我们的研究表明 tRF-1:30-Gly-GCC-2 参与了 GC 的凋亡和铁死亡。机制上，tRF-1:30-Gly-GCC-2 通过抑制丝裂原活化蛋白激酶 1() 抑制颗粒细胞增殖并促进铁死亡。tRF-1:30-Gly-GCC-2 可能成为改善卵巢功能障碍中闭锁卵泡发育的新分子靶点。总之，我们的研究为颗粒细胞功能障碍和卵泡闭锁的发病机制提供了新的视角。
