Arsenic-induced Autophagic Alterations and Mitochondrial Impairments in HPG-S Axis of Mature Male Mice Offspring (F1-generation): A persistent toxicity study.

Arsenic-induced Autophagic Alterations and Mitochondrial Impairments in HPG-S Axis of Mature Male Mice Offspring (F1-generation): A persistent toxicity study. Toxicol Lett. 2020 Feb 26;: Authors: Ommati MM, Manthari RK, Tikka C, Niu R, Sun Z, Sabouri S, Zamiri MJ, Ahmadi HN, Ghaffari H, Heidari R, Wang J Abstract Arsenic (As) has been implicated in causing reproductive toxicity, but the precise cellular pathway through which the As toxicity in mature F1- male mice hypothalamic-pituitary- gonadal- sperm (HPG-S) axis is induced has not well been documented. Hence, parental mice were treated to As2O3 (0, 0.2, 2, and 20 ppm in deionized water) from five weeks before mating until weaning, and the male pups from weaning to maturity. Afterward, the markers of oxidative stress, mitochondrial impairment, and autophagy as fundamental mechanisms of cytotoxicity and organ injury were evaluated. Higher As2O3 doses (2 and 20 ppm) were a potent inducer of oxidative stress, mitochondrial dysfunction, and autophagy in HPG-S axis. Concomitant with a dose-dependent increase in the number of MDC-labeled autophagic vacuoles in the HPG axis, an adverse dose-dependent effect was observed on the mean body weight, litter size, organ coefficient, and spermatogenesis. Transmission electron microscopy also revealed more autophagosomes at high As2O3 dosage. Concomitant with a dose-dependent increment in gene expression of PI3K, Atg5, Atg12, as well as protei...
Source: Toxicology Letters - Category: Toxicology Authors: Tags: Toxicol Lett Source Type: research
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