Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, 311300, China.
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, 311300, China.
Environ Int. 2022 Sep;167:107413. doi: 10.1016/j.envint.2022.107413. Epub 2022 Jul 16.
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 Ca 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.
全氟辛酸（PFOA）是一种广泛用作商业生产中不可或缺的表面活性剂的合成全氟化合物。由于其亲水性和持久性，PFOA 可以在生物体内积累，并在动物和人类中引起严重疾病。据报道，PFOA 暴露会影响卵巢功能并诱导生殖毒性；然而，妊娠期 PFOA 暴露对早期胚胎发育和后代的影响及其潜在机制尚不清楚。本研究发现，PFOA 暴露在体外破坏了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，从而影响了早期胚胎卵裂和囊胚形成。此外，PFOA 暴露通过诱导异常的 Ca 水平、液滴（LDs）和线粒体膜电位，在 2 细胞阶段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 细胞阶段的 DNA 损伤、自噬和细胞凋亡。妊娠期暴露于 PFOA 可显著增加 F1 后代卵巢中的细胞凋亡并破坏卵泡发育。此外，F1 后代的卵母细胞成熟能力下降。最后，单细胞转录组分析显示，PFOA 诱导的卵母细胞恶化是由 F1 后代中的线粒体功能障碍和细胞凋亡引起的。总之，我们的研究结果表明，妊娠期暴露于 PFOA 对卵巢功能具有潜在的毒性作用，并导致 F1 雌性后代中减数分裂缺陷的发生率增加。
