Perfluorohexane sulfonate (PFHxS) disturbs the estrous cycle, ovulation rate, oocyte cell communication and calcium homeostasis in mice.

Perfluoroalkyl substances are man-made chemicals with ample consumer and industrial applications. They are widely used and are resistant to environmental and metabolic degradation. Several studies have evaluated the effects of Perfluorohexane sulfonate on reproduction. However, there are few reports exploring the cell and molecular mechanisms of its toxicity in the ovary. The aim of this study was to investigate the effects of PFHxS exposure on the estrous cycle, ovulation rate, and the underlying mechanisms of action in female mice in vivo. The animals received a single sub-lethal dose of PFHxS (25.1 mg/kg, 62.5 mg/kg) or vehicle and were stimulated to obtain immature cumulus cell-oocyte complexes (COCs) from the ovaries, or superovulated to develop mature COCs. To evaluate oocyte physiology, Gap-junction intercellular communication (GJIC) was analyzed in immature COCs and calcium homeostasis was evaluated in mature oocytes. PFHxS exposure prolonged the estrous cycle and decreased ovulation rate in female mice. Connexins, Cx43 and Cx37, were downregulated and GJIC was impaired in immature COCs, providing a possible mechanism for the alterations in the estrous cycle and ovulation. No morphological abnormalities were observed in the mature PFHxS-exposed oocytes, but calcium homeostasis was affected. This effect is probably due, at least partially, to deregulation of the endoplasmic reticulum calcium modulator, Stim1. These mechanisms of ovarian injury could explain the reported correlation among PFHxS levels and subfertility in women undergoing fertility treatments.

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

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, LC50  = 269 µM) and maturation (inhibition maturation concentration IM50  = 75 µM), while in cumulus cells the LC50 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.