Aroclor 1254 impairs the development of ovarian follicles by inducing the apoptosis of granulosa cells

Aroclor 1254 impairs the development of ovarian follicles by inducing the apoptosis of granulosa cells
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Aroclor 1254 通过诱导颗粒细胞凋亡损害卵泡发育

DOI:
10.1039/c4tx00104d
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发表时间:
2015-02
影响因子:
2.1
通讯作者:
Zheng R
Zheng R
中科院分区:
医学4区
文献类型:
--
作者:
Liu SZ;Yu CN;Cheng D;Han XY;Jiang LG;Zheng R

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最近的观察表明,多氯联苯(PCBs)可以减少窦卵泡的数量,增加卵泡闭锁。然而,多氯联苯对卵泡发育各阶段的影响及其机制尚不清楚。本研究的目的是评估PCB商业混合物(Aroclor 1254)对卵泡在四个发育阶段和小鼠颗粒细胞凋亡的影响。以4、20和100 mg kg−1 b.w.的剂量通过腹腔注射给予ICR雌性小鼠Aroclor 1254。每3天1次,共5次。检测卵泡数、凋亡率及颗粒细胞超微结构。结果表明,Aroclor 1254以剂量依赖性方式减少了原始和有腔卵泡的数量,并增加了20 mg kg−1和100 mg kg−1 Aroclor 1254处理小鼠的颗粒细胞凋亡。透射电子显微镜分析显示,在用100 mg kg−1 Aroclor 1254处理的小鼠的颗粒细胞中发生线粒体功能障碍。最后,用Aroclor 1254处理小鼠显著降低了颗粒细胞中Bcl-2 mRNA的表达,并增加了Bax与Bcl-2 mRNA的比例。基于这些结果,我们得出结论,暴露于Aroclor 1254损害了卵泡(原始卵泡除外)的发育,可能是通过诱导主要在颗粒细胞中的细胞凋亡。这些结果表明,PCB污染物可能会导致人类卵巢早衰和不孕症。
Recent observations have indicated that polychlorinated biphenyls (PCBs) can reduce the number of antral follicles and increase follicular atresia. However, the effect of PCBs on follicles at each developmental stage and its underlying mechanism remain unclear. The aim of the present study was to evaluate the effects of PCB commercial mixtures (Aroclor 1254) on follicles at four developmental stages and apoptosis of mouse granulosa cells in vivo. Aroclor 1254 was administered to ICR female mice by intraperitoneal injection at the dose of 4, 20 and 100 mg kg−1 b.w. once every 3 days for five times. The number of follicles, the percentage of apoptosis and the ultrastructure of granulosa cells were determined. The results showed that Aroclor 1254 reduced the number of primordial and antral follicles in a dose-dependent manner and increased the apoptosis of granulosa cells in the mice treated with 20 mg kg−1 and 100 mg kg−1 Aroclor 1254. Transmission electron microscopy analysis showed that mitochondrial dysfunction occurred in the granulosa cells of mice treated with 100 mg kg−1 Aroclor 1254. Finally, treatment of mice with Aroclor 1254 significantly reduced the expression of Bcl-2 mRNA and increased the ratio of Bax to Bcl-2 mRNA in granulosa cells. Based on these results, we concluded that exposure to Aroclor 1254 impaired the development of follicle (primordial follicle excluded), possibly via the induction of apoptosis mainly in granulosa cells. These findings suggest that PCB pollutants may cause premature ovarian failure and infertility of humans.
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