(96) Reversal of PFOS-Induced Effects in Germ Cells with Antioxidant Treatments

A. Giri¹, R.K. Bhandari²

1.Department of Biological Science, University of Missouri, Columbia, MO 65211

2.Department of Biological Science, University of Missouri, Columbia, MO 65211

Abstract Text:

Reversal of PFOS-Induced Effects in Germ Cells with Antioxidant Treatments

A. Giri¹, R.K. Bhandari²

1.Department of Biological Science, University of Missouri, Columbia, MO 6521

2.Department of Biological Science, University of Missouri, Columbia, MO 6521

ABSTARCT

Environmental impact on reproductive cells can lead to heritable health effects which can be passed on to offspring across several generations and is found to be mediated by epigenetic processes. Environmental chemicals often induce oxidative stress which may be one of the modes of action besides their binding to the respective receptors. The use of antioxidants can ameliorate environmentally-induced health effects; however, how anti-oxidants mitigate environmental impact is not clearly understood. The present study investigated the hypothesis that environmental chemicals induce oxidative stress, and these effects impact the epigenome non-specifically through yet unknown mechanisms. Using perfluorooctane sulfonate (PFOS) as a test chemical and immortal germ cell lines (GC1 spermatogonia and GC2 spermatocytes), we examined the effects of PFOS and the mitigation potential of commercially available antioxidants to restore epigenetic changes induced by PFOS in vitro. PFOS is a widely used endocrine disrupting chemical (EDC) which is often used in industry for food packing, fire fighter foams and manufacturing of many industrial products. It is an amphiphilic chemical compound that makes it partially soluble in water as well as in lipids, as a result it gets accumulated in body which leads to production of reactive oxygen species (ROS). Firstly, we standardized the doses of PFOS and antioxidants, mainly Vitamin C, Vitamin E, and N-acetylcysteine using cell viability, oxidative stress, and gene expression analyses. PFOS induced germ cell death in a dose dependent manner possibly involving ferroptosis pathway, and the co-treatment with antioxidants blocked the PFOS-induced cell death including the reversal of the ferroptosis pathway marker expression. The blockade of cell death is accompanied by increased expression of histone modifiers (EZH1 and SUV39H) and reversal of GPX and SOD. We are currently testing if this treatment restores the DNA methylation and histone modifications in vitro and in vivo in medaka fish. The present findings indicate epigenetic modifications caused by PFOS may be minimized with antioxidant treatments, suggesting the possibility for intervention of inter- and transgenerational impacts of PFOS.