Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
Mol Cell Endocrinol. 2022 Mar 1;543:111550. doi: 10.1016/j.mce.2021.111550. Epub 2022 Jan 4.
Autophagy of granulosa cell (GC) may be a supplementary mechanism involved in follicular atresia through cooperating with apoptosis. Leukemia inhibitory factor (LIF) has been shown to promote follicular growth, through the underlying molecular mechanisms remain unclear. Rapamycin, an autophagy inducer, triggered the elevation of GC apoptosis within follicles, and then prevented follicular growth. However, combined treatment with LIF relieved the follicular regression caused by rapamycin, mainly resulting in alleviating the decline of GCs viability and cell autophagic apoptosis, and eventually, promoting follicle development. Further investigation revealed that LIF inhibited the GC autophagic apoptosis by activating PI3K/AKT and Stat3 pathways, reflecting an increase of BCL-2 expression but a decrease in BECN1. Additionally, blocking PI3K/AKT and Stat3 pathways resulted in the reduction of LIF protection against follicular atresia. These findings illustrated that LIF activated the PI3K/AKT and Stat3 signaling pathways to inhibit GC autophagic cell death, and further relieve chicken follicular atresia.
颗粒细胞（GC）的自噬可能是通过与细胞凋亡协同作用参与卵泡闭锁的补充机制。白血病抑制因子（LIF）已被证明可通过尚未阐明的潜在分子机制促进卵泡生长。雷帕霉素是一种自噬诱导剂，可引发卵泡内 GC 凋亡增加，进而阻止卵泡生长。然而，LIF 与雷帕霉素联合治疗缓解了由雷帕霉素引起的卵泡退化，主要表现为减轻 GC 活力和细胞自噬凋亡的下降，最终促进卵泡发育。进一步的研究表明，LIF 通过激活 PI3K/AKT 和 Stat3 通路抑制 GC 自噬性细胞凋亡，反映出 BCL-2 表达增加而 BECN1 减少。此外，阻断 PI3K/AKT 和 Stat3 通路会降低 LIF 对卵泡闭锁的保护作用。这些发现表明，LIF 激活了 PI3K/AKT 和 Stat3 信号通路，抑制了 GC 的自噬性细胞死亡，从而进一步缓解了鸡卵泡的闭锁。
