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

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.

Adverse PFAS effects on mouse oocyte in vitro maturation are associated with carbon-chain length and inclusion of a sulfonate group

“…We next selected 600 µM PFHxS and PFOS to study their toxic mechanisms. First, we observed mitochondrial dysfunction including an increased intracellular ROS level and diminishing MMP in PFHxS- and PFOS-treated oocytes, which have been reported for other types of PFAS like PFNA and PFOA, both in vivo 19–21 and in vitro 64 . For PFOS exposure, Wei et al also measured the expression of antioxidant enzyme levels inside oocytes.…”

“…For all cells that undergo aerobic respiration, redox homeostasis is maintained between the ROS generation and scavenging. 35 Various PFAS chemicals have been reported to break the redox balance in mouse oocytes, including PFNA 20 , PFOS 19 , and PFOA 21 . Excess ROS induces oxidative stress, leading to DNA damage, protein malfunction, and lipid chain breakage.…”

“…Various epigenetic regulations are known to be involved in oocyte maturation, including histone acetylation, phosphorylation, and SUMOylation. 15 GVBD, the breakdown of nuclear envelop, exposes the chromosomes to many environmental toxicants, such as iodoacetic acid (IAA) 16 , PM 17 and several PFAS chemicals 18–21 . IAA, for example, has been shown to induce DNA damage and cause chromosome misalignment at the metaphase I stage.…”

Perfluorooctanoic acid exposure in vivo perturbs mitochondrial metabolic during oocyte maturation

“…In addition, PFOA exposed to Ishikawa cells was found to have endocrine disrupting activity in endometrial function through significant gene cascade dysregulation 23 . In addition, exposure of oocytes to PFOA in vitro has been reported to negatively affect oocyte maturation and induce a series of reactions such as oxidative stress 24,25 . However, there have been few studies on maternal exposure to PFOA before pregnancy.…”

“…It is well recognized that any mistakes in this process can increase aneuploid embryos rates, which leads to pregnancy loss or congenital disabilities. In addition, exposure of oocytes to PFOA in vitro has been reported to negatively affect oocyte maturation and induce a series of reactions such as oxidative stress 24 . However, there have been few studies on maternal exposure to PFOA before pregnancy.…”