Perfluorooctanoic acid exposure in vivo perturbs mitochondrial metabolic during oocyte maturation

Abstract

Perfluorooctanoic acid (PFOA), a member of a group of polyfluorinated and perfluorinated alkyl substances (PFAS), is associated with adverse pregnancy outcomes in mammals. However, the effects of in vivo exposure to PFOA on the female reproductive system and the underlying mechanisms remain unclear. In our study, we constructed a mouse model to investigate whether low-dose PFOA (1 mg/kg/day) or high-dose PFOA (5 mg/kg/day) affect meiosis maturation of oocytes and the potential mechanisms that may be associated with oocyte maturation disorder. Our results indicate that low-dose and high-dose PFOA can lead to impaired oocyte maturation, which is manifested by decreased rate of embryonic foam rupture and first polar body extrusion. Moreover, PFOA exposure harmed the mitochondrial metabolic, resulting in low levels of ATP contents, high reactive oxygen species, aberrant mitochondrial membrane potential. In addition, the proportion of DNA damage marker γ-H2AX was also significantly increased in PFOA exposure oocytes. These changes lead to abnormal arrangements of the spindle and chromosomes during oocyte maturation. In conclusion, our results for the first time illustrated that exposure to PFOA in vivo in female mice impaired the meiosis maturation of oocytes, which provided a basis for studying the mechanism of PFOA reproductive toxicity in female mammals.

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

“…The role of PFAS in peri‐and postnatal development and pregnancy outcomes was reported recently for example exposure of a human trophoblast (JEG3) cell line to PFOS, and PFOA showed modest alteration of gene expression that is involved in trophoblast viability, syncytialization transport, invasion/mesenchymal transition, inflammation, and apoptosis indicates that PFAS dysregulate placentation by affecting trophoblast 65 . Exposure of female mice to PFOA (5 mg/kg/day) impaired the meiosis maturation of oocytes by decreasing the rate of embryonic foam rupture and first polar body extrusion 66 . 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 .…”

“… 66 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.…”

“…P<0.001 65 Exposure of female mice to PFOA (5 mg/kg/day) impaired the meiosis maturation of oocytes by decreasing the rate of embryonic foam rupture and first polar body extrusion. 66 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.…”

Perfluorooctanoic Acid (PFOA) Exposure Compromises Fertility by Affecting Ovarian and Oocyte Development

“…Previous studies have reported that PFOA can cross the blood–follicle barrier and is more likely to come in contact with and damage oocytes directly, which suggests PFOA is linked to poor fertility [ 31 , 32 ]. In addition, animal experiments have indicated that PFOA exposure causes a decline in the number of follicles by impairing the meiosis of oocytes [ 33 ].…”

How Per- and Poly-Fluoroalkyl Substances Affect Gamete Viability and Fertilization Capability: Insights from the Literature

“…Mitochondria are the biggest producer of reactive oxygen species (ROS) as they regulate energy through oxidative phosphorylation [ 52 ]. ROS are a group of oxygen-containing species that are highly reactive and are a normal by-product of metabolism and cellular processes [ 51 ].…”