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全氟辛酸通过触发线粒体和 DNA 损伤来抑制体外培养的小鼠卵母细胞的成熟率。

Perfluorooctanoic acid inhibits the maturation rate of mouse oocytes cultured in vitro by triggering mitochondrial and DNA damage.

机构信息

National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China.

Guangdong Province Key Laboratory of Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China.

出版信息

Birth Defects Res. 2021 Aug 15;113(14):1074-1083. doi: 10.1002/bdr2.1899. Epub 2021 Apr 19.

Abstract

BACKGROUND

Perfluorooctanoic acid (PFOA) is widely used in the manufacture of household and industrial products. It has certain toxicity and leaves many residues in the environment. Numerous studies have shown that PFOA exhibits endocrine disrupting properties and immunotoxicity and induces developmental defects. However, there is very little information regarding its toxicity on oocytes.

METHODS

We cultured denuded oocytes in maturation medium supplemented with 0, 300, or 500 PFOA during IVM and evaluated the maturation of oocytes from the aspects of ROS(DCFH-DA), mitochondria(MitoOrange and JC-1), DNA damage(P-H2AX), and cytoskeleton(β-tubulin).

RESULTS

Compared with the control group, the PFOA treatment group exhibited significantly reduced proportion of oocytes matutation. Furthermore, the DCFH-DA test showed that PFOA significantly increased reactive oxygen species (ROS) levels. PFOA disrupted mitochondrial distribution and decreased mitochondrial function as assessed using MitoOrange and JC-1. In addition, PFOA-treated oocytes exhibited a significantly higher percentage of P-H2AX, defective β-tubulin, abnormal chromosome alignment, lower expression of the anti-apoptotic gene Bcl-2, and higher expression of the apoptotic genes caspase3 and Bax.

CONCLUSION

In summary, PFOA could negatively and directly affect oocyte maturation in vitro and cause oxidative stress, mitochondrial function disruption, DNA damage, cytoskeleton damage, and apoptosis.

摘要

背景

全氟辛酸(PFOA)广泛用于家庭和工业产品的制造。它具有一定的毒性,并且在环境中留下许多残留物。许多研究表明,PFOA 具有内分泌干扰特性和免疫毒性,并诱导发育缺陷。但是,关于其对卵母细胞的毒性的信息却很少。

方法

我们在 IVM 期间将去卵丘卵母细胞培养在补充有 0、300 或 500 PFOA 的成熟培养基中,并从 ROS(DCFH-DA),线粒体(MitoOrange 和 JC-1),DNA 损伤(P-H2AX)和细胞骨架(β-微管蛋白)方面评估卵母细胞的成熟情况。

结果

与对照组相比,PFOA 处理组卵母细胞的成熟比例明显降低。此外,DCFH-DA 测试表明 PFOA 显着增加了活性氧(ROS)水平。PFOA 破坏了线粒体的分布并降低了线粒体的功能,这可以通过 MitoOrange 和 JC-1 进行评估。此外,用 PFOA 处理的卵母细胞中 P-H2AX,β-微管蛋白缺陷,染色体排列异常,抗凋亡基因 Bcl-2 的表达降低以及凋亡基因 caspase3 和 Bax 的表达升高的比例明显更高。

结论

综上所述,PFOA 可能会对体外卵母细胞成熟产生负面影响,并直接导致氧化应激,线粒体功能障碍,DNA 损伤,细胞骨架损伤和细胞凋亡。

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