Wu Hao, Han Yingxue, Liu Jikang, Zhao Rong, Dai Shizhen, Guo Yajun, Li Nan, Yang Feng, Zeng Shenming
National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Department of Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
J Anim Sci Biotechnol. 2024 Nov 5;15(1):147. doi: 10.1186/s40104-024-01107-3.
Follicular atresia significantly impairs female fertility and hastens reproductive senescence. Apoptosis of granulosa cells is the primary cause of follicular atresia. Pyroptosis and necroptosis, as additional forms of programmed cell death, have been reported in mammalian cells. However, the understanding of pyroptosis and necroptosis pathways in granulosa cells during follicular atresia remains unclear. This study explored the effects of programmed cell death in granulosa cells on follicular atresia and the underlying mechanisms.
The results revealed that granulosa cells undergo programmed cell death including apoptosis, pyroptosis, and necroptosis during follicular atresia. For the first time, we identified the formation of a PANoptosome complex in porcine granulosa cells. This complex was initially identified as being composed of ZBP1, RIPK3, and RIPK1, and is recruited through the RHIM domain. Additionally, we demonstrated that caspase-6 is activated and cleaved, interacting with RIPK3 as a component of the PANoptosome. Heat stress may exacerbate the activation of the PANoptosome, leading to programmed cell death in granulosa cells.
Our data identified the formation of a PANoptosome complex that promoted programmed cell death in granulosa cells during the process of follicular atresia. These findings provide new insights into the molecular mechanisms underlying follicular atresia.
卵泡闭锁显著损害女性生育能力并加速生殖衰老。颗粒细胞凋亡是卵泡闭锁的主要原因。细胞焦亡和坏死性凋亡作为程序性细胞死亡的其他形式，已在哺乳动物细胞中有所报道。然而，卵泡闭锁过程中颗粒细胞内细胞焦亡和坏死性凋亡途径仍不清楚。本研究探讨了颗粒细胞程序性细胞死亡对卵泡闭锁的影响及其潜在机制。
结果显示，在卵泡闭锁过程中颗粒细胞会经历包括凋亡、细胞焦亡和坏死性凋亡在内的程序性细胞死亡。我们首次在猪颗粒细胞中鉴定出PANoptosome复合体的形成。该复合体最初被确定由ZBP1、RIPK3和RIPK1组成，并通过RHIM结构域募集。此外，我们证明了caspase-6被激活并裂解，作为PANoptosome的一个组成部分与RIPK3相互作用。热应激可能会加剧PANoptosome的激活，导致颗粒细胞程序性细胞死亡。
我们的数据确定了PANoptosome复合体的形成，该复合体在卵泡闭锁过程中促进了颗粒细胞的程序性细胞死亡。这些发现为卵泡闭锁的分子机制提供了新的见解。
