Abstract：
4-Vinylcyclohexene diepoxide (VCD) is a potentially hazardous industrial chemical that may enter a goat\'s body in various ways during industrial breeding. Ovarian granulosa cells (GCs) play a critical role in supporting follicle development and hormone synthesis. However, there are few studies on the effect of VCD on goat ovarian GCs. In this study, goat ovarian GCs were isolated and treated with VCD. The results showed that treatment with VCD increased the proportion of S phase and G2/M cells, but decreased the proportion of G1 phase. VCD treatment significantly inhibited the expression of cyclin A and cyclin-dependent kinase 2 (CDK2). But the expression levels of p21 and p27 were increased. VCD could induce an apparent increase in the proportion of apoptosis and the level of cleaved caspase 3. Treatment with VCD significantly reduced the progesterone and estrogen concentration in the medium in which goat ovarian GCs were cultured. Correspondingly, the expression level of steroidogenic acute regulatory protein (STAR) was significantly downregulated. Treatment with 0.25 and 0.5 mM VCD, the protein expression level of insulin-like growth factor 1 receptor (IGF1R) and Akt were significantly decreased. Moreover, treatment with 0.25 mM VCD significantly inhibited the phosphorylation of Akt. In conclusion, VCD exposure had cytotoxic effects such as decreased cell viability, disordered cell cycle, increased apoptosis, and interference with steroid hormone synthesis on goat GCs. These cytotoxic effects of VCD on goat GCs may be due to the downregulation of IGF1R and the inhibition of IGF1R/Akt signaling pathway.
摘要：
4-乙烯基环己烯二环氧化物（VCD）是一种潜在危险的工业化学品，在工业育种过程中可能以各种方式进入山羊体内。卵巢颗粒细胞（GC）在支持卵泡发育和激素合成中起关键作用。然而,关于VCD对山羊卵巢GCs影响的研究很少。在这项研究中,分离山羊卵巢GCs并用VCD处理。结果表明，VCD处理增加了S期和G2/M期细胞的比例，但降低了G1期的比例。VCD处理显著抑制细胞周期蛋白A和细胞周期蛋白依赖性激酶2(CDK2)的表达。但p21和p27的表达量均有所增长。VCD可以诱导凋亡比例和caspase3裂解水平的明显增加。用VCD处理可显着降低培养山羊卵巢GC的培养基中的孕酮和雌激素浓度。相应地,类固醇急性调节蛋白（STAR）的表达水平显着下调。用0.25和0.5mMVCD治疗，胰岛素样生长因子1受体(IGF1R)和Akt蛋白表达水平显著降低。此外，用0.25mMVCD处理显著抑制Akt的磷酸化。总之,VCD暴露具有细胞毒性作用，例如降低细胞活力，细胞周期紊乱，细胞凋亡增加，并干扰山羊GC的类固醇激素合成。VCD对山羊GC的这些细胞毒性作用可能是由于IGF1R的下调和IGF1R/Akt信号通路的抑制。
