Synergistic effects of arsenic and fluoride on oxidative stress and apoptotic pathway in Leydig and Sertoli cells

Abstract

Excessive intake of arsenic (As) and fluoride (F), which are present in underground drinking water, have adverse effects on human health, and especially on the male reproductive system. In this regard, it's critical to figure out how As and F affect Leydig and Sertoli cells, which are key cells in the male reproductive system. The goal of this study was to determine the synergistic effects of co-exposure of As and F, via drinking water, on Leydig and Sertoli cells, which are models for the male reproductive system, as well as the mechanisms underlying these effects in terms of oxidative damage and apoptosis. Leydig and Sertoli cells were exposed to concentrations of 7.7 µM (0.57 ppm) As and 0.4 mM (7.24 ppm) F based on the highest daily intake of drinking water for 24 h. The present results revealed that As and/or F treatment reduced cell viability and proliferation in Leydig and Sertoli cells, elevated lactate dehydrogenase, a cytotoxicity marker, and triggered oxidative stress and apoptosis. Furthermore, it has been proven that when As and F are exposed in combination, they have a synergistic effect. In conclusion, by revealing the harmful effects of As and F on Leydig and Sertoli cells, and thus on male infertility, it is possible to reduce As and F exposure to prevent infertility after exposure to these molecules not only separately but also together. It will be considered to determine new action and action plans to reduce As and F exposure.