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.

全氟辛酸 (PFOA) 是一种合成的全氟化合物，广泛用作商业生产中的整体表面活性剂。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诱发严重疾病。据报道，PFOA 暴露会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后代的影响和潜在机制仍不清楚。这项研究发现，在小鼠早期胚胎第一次卵裂期间，体外暴露 PFOA 会破坏纺锤体组装和染色体排列，从而影响早期胚胎卵裂和囊胚形成。此外，PFOA 暴露通过诱导异常 Ca²⁺水平、液滴 (LD) 和 2 细胞阶段的线粒体膜电位。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 显着增加了 F1 后代的卵巢凋亡并破坏了卵泡发育。此外，F1 后代的卵母细胞成熟能力下降。最后，单细胞转录组分析表明，PFOA 诱导的卵母细胞退化是由 F1 后代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 对卵巢功能有潜在的毒性影响，并导致 F1 雌性后代减数分裂缺陷的发生率更高。