Perfluorooctanoic acid (PFOA) exposure affects early embryonic development and offspring oocyte quality via inducing mitochondrial dysfunction.
Perfluorooctanoic acid (PFOA) exposure affects early embryonic development and offspring oocyte quality via inducing mitochondrial dysfunction.
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全氟辛酸（PFOA）暴露通过诱导线粒体功能障碍影响早期胚胎发育和后代卵母细胞质量。
DOI：
10.1016/j.envint.2022.107413
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发表时间：
2022-07
影响因子：
11.8
通讯作者：
Yu-ting Zhou;Rui Li;Si-Hong Li;Xiang Ma;Lu Liu;Dong Niu;Xing Duan
中科院分区：
文献类型：
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作者：
Yu-ting Zhou;Rui Li;Si-Hong Li;Xiang Ma;Lu Liu;Dong Niu;Xing Duan
全氟辛酸（PFOA）是一种合成的全氟化合物，在商业生产中广泛用作整体表面活性剂。由于其亲水性和持久性，PFOA可在生物体中积累并诱发动物和人类的严重疾病。据报道，PFOA暴露可影响卵巢功能并诱发生殖毒性；然而，妊娠期PFOA暴露对早期胚胎发育和子代的影响及其潜在机制尚不清楚。本研究发现，PFOA体外暴露会破坏早期小鼠胚胎第一次卵裂过程中的纺锤体组装和染色体排列，从而影响早期胚胎的卵裂和囊胚的形成。此外，PFOA暴露通过诱导2细胞期异常的Ca2+水平、液滴（LDs）和线粒体膜电位引起线粒体功能障碍和氧化应激。此外，我们发现PFOA暴露通过抑制SOD2功能导致2细胞期DNA损伤、自噬和凋亡。妊娠期暴露于PFOA显著增加F1后代卵巢凋亡和卵泡发育中断。此外，F1后代的卵母细胞成熟能力降低。最后，单细胞转录组分析显示，pfoa诱导的卵母细胞退化是由线粒体功能障碍和凋亡引起的。总之，我们的研究结果表明，妊娠期暴露于PFOA对卵巢功能有潜在的毒性作用，并导致F1雌性后代减数分裂缺陷的发生率更高。
Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated compound that is extensively used as an integral surfactant in commercial production. Owing to its hydrophilicity and persistence, PFOA can accumulate in living organisms and induce severe disease in animals and humans. It has been reported that PFOA exposure can affect ovarian function and induce reproductive toxicity; however, the effects and potential mechanism of PFOA exposure during gestation on early embryonic development and offspring remain unclear. This study found that PFOA exposure in vitro disrupted spindle assembly and chromosome alignment during the first cleavage of early mouse embryos, which impacted early embryonic cleavage and blastocyst formation. Moreover, PFOA exposure caused mitochondrial dysfunction and oxidative stress by inducing aberrant Ca2+levels, liquid drops(LDs), and mitochondrial membrane potential in the 2-cell stage. Furthermore, we found that PFOA exposure resulted in DNA damage, autophagy, and apoptosis in 2-cell stage by inhibiting SOD2 function. Gestational exposure to PFOA significantly increased ovarian apoptosis and disrupted follicle development in F1 offspring. In addition, oocyte maturation competence was decreased in F1 offspring. Finally, single-cell transcriptome analysis revealed that PFOA-induced oocyte deterioration was caused by mitochondrial dysfunction and apoptosis in the F1 offspring. In summary, our results indicated that gestational exposure to PFOA had potential toxic effects on ovarian function and led to a higher incidence of meiotic defects in F1 female offspring.