Perfluorooctanoic acid (PFOA) exposure affects early embryonic development and offspring oocyte quality via inducing mitochondrial dysfunction

• Published in: Environment international Vol. 167; p. 107413
• Main Authors: Zhou, Yu-Ting, Li, Rui, Li, Si-Hong, Ma, Xiang, Liu, Lu, Niu, Dong, Duan, Xing
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.09.2022; Elsevier
• Subjects: Apoptosis; Autophagy; blastocyst; calcium; chromosomes; disease severity; DNA damage; Early embryonic development; embryogenesis; environment; females; hydrophilicity; liquids; maternal exposure; meiosis; membrane potential; mice; Mitochondria; mitochondrial membrane; oocytes; oxidative stress; perfluorocarbons; perfluorooctanoic acid; PFOA; pregnancy; progeny; reproductive toxicology; surfactants; toxicity; transcriptomics; Early embryonic development; Mitochondria; PFOA; Autophagy; Apoptosis
• ISSN: 0160-4120; 1873-6750; 1873-6750
• DOI: 10.1016/j.envint.2022.107413

[Display omitted] •PFOA exposure has adverse effect on early embryonic development.•PFOA exposure induces mitochondrial dysfunction in 2-cell stage.•PFOA exposure produces excessive ROS to induce the occurrence of autophagy and apoptosis.•Gestational exposure to PFOA has potential toxic effects on ovarian function and lead to a higher incidence of meiotic defects in F1 female offspring. 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.