PDF(Pubmed)
Abstract：
Atresia is a process in ovarian follicles that is regulated by hormone-induced apoptosis. During atresia, granulosa cell (GC) apoptosis is a key mechanism orchestrated through diverse signaling pathways. Cocaine- and amphetamine-regulated transcript (CART) signaling within ovarian GCs has been demonstrated to play a key role in the regulation of follicular atresia in cattle, pigs, and sheep. The present work aimed to investigate the potential local regulatory role of CART in GC apoptosis-induced follicular atresia in buffalo, focusing on the modulation of the AKT/GSK3β/β-catenin signaling pathways, which are the intracellular signaling pathways involved in cell viability. Our findings revealed increased expression of CARTPT and BAX and decreased levels of AKT, β-catenin, and CYP19A1 genes in atretic follicles compared to healthy follicles. Subsequently, CART treatment in the presence of FSH inhibited the FSH-induced increase in GC viability by reducing estradiol production and increasing apoptosis. This change was accompanied by an increase in the gene expression levels of both CARTPT and BAX. At the protein level, treatment with CART in the presence of FSH negatively affected the activity of AKT, β-catenin, and LEF1, while the activity of GSK3β was enhanced. In conclusion, our study shows how CART negatively influences buffalo GC viability, underlying the modulation of the AKT/GSK3β/β-catenin pathway and promoting apoptosis-a key factor in follicular atresia.
摘要：
闭锁是卵巢卵泡中由激素诱导的细胞凋亡调节的过程。在闭锁期间，颗粒细胞（GC）凋亡是通过多种信号通路协调的关键机制。已证明卵巢GCs中的可卡因和苯丙胺调节的转录物（CART）信号在牛卵泡闭锁的调节中起关键作用，猪,和羊。本研究旨在探讨CART在水牛GC凋亡诱导的卵泡闭锁中的潜在局部调节作用。关注AKT/GSK3β/β-catenin信号通路的调制，它们是参与细胞活力的细胞内信号通路。我们的发现表明CARTPT和BAX的表达增加，AKT水平降低，β-连环蛋白，与健康卵泡相比，闭锁卵泡中的CYP19A1基因。随后，在FSH存在下的CART处理通过减少雌二醇产生和增加细胞凋亡来抑制FSH诱导的GC活力增加。这种变化伴随着CARTPT和BAX的基因表达水平的增加。在蛋白质水平，在FSH存在下用CART治疗会对AKT的活性产生负面影响，β-连环蛋白，和LEF1，而GSK3β的活性增强。总之,我们的研究表明CART如何负面影响水牛GC的生存能力，AKT/GSK3β/β-catenin通路的调节和促进细胞凋亡是卵泡闭锁的关键因素。
