(102) Oxidative Stress- An Intermediate Step for the PFOS exposure-induced Epigenetic Effects in Sertoli and Leydig cells

J. Nath, R. K. Bhandari

Division of Biological Sciences, University of Missouri, Columbia, MO 65211

Abstract Text:

Environmental chemicals often induce oxidative stress accompanied by altered epigenomic and transcriptomic landscapes leading to endocrine disruption. Disruption of signaling system in the testicular somatic cells, Sertoli and Leydig cells, results in male fertility issues. Perfluorooctane sulfonic acid (PFOS) is an emerging threat to ecosystem because of its prolonged half-life. Globally, PFOS has been found in breast milk, blood, amniotic fluid, and semen. PFOS can induce reproductive impairments in males by directly interacting with Sertoli cells and affecting tight junctions and cellular signaling pathways. It is not clearly understood whether PFOS exposure-induced oxidative stress impairs Sertoli and Leydig cell function through alteration in their epigenetic landscape. Using the TM3 and TM4 cell lines (mouse), we examined if PFOS-induced cell death involves oxidative stress and ferroptosis-mediated epigenetic alterations. The dosing concentration of PFOS and antioxidants, mainly vitamin C, vitamin D, vitamin E, N-acetyl cysteine, and hesperidin, were chosen based on cell viability outcomes. The antioxidants, mainly vitamin C, vitamin D, vitamin E, N-acetyl cysteine, and hesperidin, blocked the PFOS-induced cell death and decreased mRNA levels of ferroptosis markers. Gene expression results suggest that PFOS can induce DNA methylation and H3K9 trimethylation which can be reversed by selected antioxidant treatments. The present study suggests that PFOS-induced toxicity involves elevated levels of oxidative stress, and the antioxidant co-treatments ameliorate cellular toxicity along with erasure of PFOS-induced epigenetic memory in vitro. The study provides significant insights into mitigation of endocrine disruptor-induced reproductive impairments in males. The research was supported by the Mizzou Forward Initiative of the University of Missouri to RKB.