Paternal exposure to arsenic resulted in oxidative stress, autophagy, and mitochondrial impairments in the HPG axis of pubertal male offspring

Despite the knowledge of AS-induced reprotoxicity, the literature concerning arsenic trioxide (As2O3)-induced oxidative stress and consequent intracellular events, like autophagy process, in the hypothalamic-pituitary- gonadal (HPG) axis of F1- pubertal male mice is sparse to date. Hence, we made an attempt to study the reproductive toxicities and the underlying mechanisms induced by As2O3 in the HPG axis of pubertal F1- male mice in correlation with oxidative stress-induced autophagy. Parental mice were challenged with As2O3 (0, 0.2, 2, and 20 ppm) from five weeks before mating, and continued till puberty age for the male pups. It was recorded that higher As2O3 doses (2 and 20 ppm) were a potent inducer of oxidative stress and autophagy in the HPG axis. Concomitant with a decrease on mean body weight, total antioxidant capacity, and stereology indices, an increase in the number of MDC-labeled autophagic vacuoles, and MDA/GSH ratio in HPG axis of pubertal F1- male mice which were exposed to higher As2O3 doses was observed. Meanwhile, concomitant with a dose-dependent increment in the gene expression of ATG3, ATG5, Beclin, as well as protein expression of P62, ATG12, and Beclin in HPG axis tissues; a dose-dependent decrease in PI3K and mTOR gene expression was recorded in the HPG tissues of pubertal F1-males. Altogether, our observations suggest that higher doses of As2O3 have detrimental effects on the functionality of HPG axis in pubertal male mice offspring by increasing MDA/GSH ratio and autophagic cell death-related genes and proteins, as well as by reducing total antioxidant capacity. •Arsenic induced reproductive toxicity in pubertal F1-male generation whose parents and themselves challenged with higher As2O3 doses.•Mean body weight, total antioxidant capacity, and stereology indices were adversely changed in the HPG axis of pubertal F1- male mice.•The MDA/GSH ratio and the number of MDC-labeled autophagic vacuoles in the HPG axis of pubertal F1- male mice exposing to higher As2O3 doses were considerably increased.•A dose-dependent increase in Beclin, ATG3, and ATG5 gene expression, as well as Beclin, P62, and ATG12 protein expression in the HPG axis tissues of pubertal F1-males were recorded.•A dose-dependent decrement in the gene expression of mTOR and PI3K was observed in the HPG tissues of pubertal F1-males exposing to higher As2O3 doses.