Continuous gibberellin A3 exposure from weaning to sexual maturity induces ovarian granulosa cell apoptosis by activating Fas-mediated death receptor signaling pathways and changing methylation patterns on caspase-3 gene promoters,Toxicology Letters

当前位置： X-MOL 学术 › Toxicol. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Continuous gibberellin A3 exposure from weaning to sexual maturity induces ovarian granulosa cell apoptosis by activating Fas-mediated death receptor signaling pathways and changing methylation patterns on caspase-3 gene promoters
Toxicology Letters ( IF 2.9 ) Pub Date : 2020-02-01 , DOI: 10.1016/j.toxlet.2019.11.012
Yiwei Guo ₁ , Wenxiang Wang ₁ , Yiqin Chen ₁ , Yan Sun ₂ , Yuchen Li ₃ , Fangyuan Guan ₄ , Qi Shen ₄ , Yiruo Guo ₄ , Wenchang Zhang ₃

Affiliation

Information on the effects of gibberellic acid (gibberellin A3, GA3) on ovarian follicle development is limited. In our present study, 21-day-old female Wistar rats were exposed to GA3 by gavage (25, 50, and 100 mg/kg body weight, once per day) for eight weeks to evaluate the influence of GA3 on ovarian follicle development. After treatment, significant (P < 0.05) increases (to 40.17% and 44.5%, respectively) in atretic follicle proportions and significant decreases (to 19.49% and 17.86%, respectively) in corpus luteum proportions were observed in the 50 and 100 mg/kg treatment groups compared to the control group. Significant (P < 0.05) increases (to 31.3% and 42.0%, respectively) in follicle apoptosis were observed in the 50 and 100 mg/kg treatment groups by transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Significantly increased expression of caspase-3, caspase-8, caspase-9 and Fas was observed by real-time PCR and Western blotting. Bisulfite sequencing PCR (BSP) revealed obviously decreased total methylation percentages of the caspase-3 promoter region in the two treatment groups. Real-time quantitative PCR also showed significantly decreased mRNA expression of DNA methyltransferase (Dnmt) 3a and Dnmt3b. Further in vitro studies showed that a DNA methylation inhibitor could enhance the GA3-induced increase in the mRNA expression of caspase-3. Overall, our present study indicates that GA3 administration from weaning until sexual maturity can affect ovarian follicle development by inducing apoptosis and suggests that signaling through the Fas-mediated apoptotic pathway may be an important underlying mechanism of this apoptosis. In addition, GA3-induced aberrant DNA methylation patterns might be partly responsible for upregulation of caspase-3 gene expression.

中文翻译：

从断奶到性成熟期间持续接触赤霉素 A3，通过激活 Fas 介导的死亡受体信号通路和改变 caspase-3 基因启动子上的甲基化模式，诱导卵巢颗粒细胞凋亡

关于赤霉酸（赤霉素 A3、GA3）对卵泡发育影响的信息有限。在我们目前的研究中，21日龄雌性Wistar大鼠通过灌胃法暴露于GA3（25、50和100 mg/kg体重，每天一次）八周，以评估GA3对卵巢卵泡发育的影响。治疗后，50 和 100 mg/ 组观察到闭锁卵泡比例显着增加（分别为 40.17% 和 44.5%），黄体比例显着降低（分别为 19.49% 和 17.86%）。 kg 治疗组与对照组相比。通过透射电子显微镜和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 测定，在 50 和 100 mg/kg 治疗组中观察到卵泡细胞凋亡显着（P < 0.05）增加（分别达到 31.3% 和 42.0%）。通过实时 PCR 和蛋白质印迹观察到 caspase-3、caspase-8、caspase-9 和 Fas 的表达显着增加。亚硫酸氢盐测序 PCR (BSP) 显示两个处理组中 caspase-3 启动子区域的总甲基化百分比明显降低。实时定量 PCR 还显示 DNA 甲基转移酶 (Dnmt) 3a 和 Dnmt3b 的 mRNA 表达显着降低。进一步的体外研究表明，DNA 甲基化抑制剂可以增强 GA3 诱导的 caspase-3 mRNA 表达增加。总体而言，我们目前的研究表明，从断奶到性成熟期间施用 GA3 可以通过诱导细胞凋亡来影响卵泡发育，并表明通过 Fas 介导的细胞凋亡途径发出的信号可能是这种细胞凋亡的重要潜在机制。此外，GA3 诱导的异常 DNA 甲基化模式可能是 caspase-3 基因表达上调的部分原因。

更新日期：2020-02-01

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11