Effects of perfluorooctanoic acid in oxidative stress generation, DNA damage in cumulus cells, and its impact on in vitro maturation of porcine oocytes

Abstract

Perfluorooctanoic acid is a synthetic compound mostly used in a wide range of consumer products with several adverse effects on somatic cells and gametes. It has been linked to hepatotoxic and carcinogenic effects, alterations in the immune system, endocrine, and reproductive alterations. In vivo studies show an increase in reactive oxygen species and DNA damage. However, the mechanisms by which this compound affects fertility, remain contradictory. Therefore, the aim of the present study was to evaluate the effect of perfluorooctanoic acid on oocyte viability and maturation, as well as the viability, generation of oxidative stress, and genotoxic damage in the cumulus cells exposed during in vitro maturation. This compound had a negative effect on oocyte viability (lethal concentration, LC 50 = 269 μM) and maturation (inhibition maturation concentration IM 50 = 75 μM), while in cumulus cells the LC 50 was 158 μM. The generation of reactive oxygen species evaluated in cumulus cells, protein carbonylation, and DNA damage, was significantly increased at 40 μM perfluorooctanoic acid. This study provides evidence that perfluorooctanoic acid causes reactive oxygen species generation, protein oxidation, and DNA damage in cumulus cells, compromising the maturation and viability of porcine oocyte, which may affect fertility.

Per‐ and polyfluoroalkyl substances activate UPR pathway, induce steatosis and fibrosis in liver cells

“…PFOA affects mitochondrial metabolic activities/membrane potential and produced low levels of ATP and high reactive oxygen species (ROS) in oocytes suggesting that PFOA enhanced reproductive toxicity in female mice 66 . Similarly, exposure to PFOA affects porcine oocyte maturation, and exposure to PFOA enhanced reactive oxygen species production, protein carbonylation, and DNA damage in cumulus cells 67 . Administration of perfluorotridecanoic acid (PFTrDA) to pregnant Sprague–Dawley female rats showed decreased serum testosterone levels at 1 mg/kg and also promoted abnormal aggregation of fetal Leydig cells at doses of 5 and 10 mg/kg 68 .…”

“… 66 Similarly, exposure to PFOA affects porcine oocyte maturation, and exposure to PFOA enhanced reactive oxygen species production, protein carbonylation, and DNA damage in cumulus cells. 67 Administration of perfluorotridecanoic acid (PFTrDA) to pregnant Sprague–Dawley female rats showed decreased serum testosterone levels at 1 mg/kg and also promoted abnormal aggregation of fetal Leydig cells at doses of 5 and 10 mg/kg. 68 PFTrDA also down‐regulated fetal Leydig cell (FLC) genes such as Insl3 , Lhcgr , Scarb1 , Nr5a1 , Cyp17a1 , Star , Hsd3b1 , and Dhh , antioxidants ( GPX1 , SOD1 , CAT ) and induced autophagy suggesting that PFTrDA inhibits the differentiation of fetal Leydig cells in male pups.…”

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.…”

“…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. In addition, the underlying mechanism is still unclear.…”