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Paternal Exposure to Arsenic Resulted in Oxidative Stress, Autophagy, and Mitochondrial Impairments in the Hpg-S Axis of Pubertal Male Offspring Publisher Pubmed



Ommati MM1, 2 ; Heidari R3 ; Manthari RK1 ; Tikka SCJ1 ; Niu R1 ; Sun Z1 ; Sabouri S1 ; Zamiri MJ4 ; Zaker L5 ; Yuan J1, 2 ; Wang J1 ; Zhang J1
Authors
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Authors Affiliations
  1. 1. Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, China
  2. 2. College of Life Sciences, Shanxi Agricultural University, Taigu, 030801, Shanxi, China
  3. 3. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, 158371345, Iran
  4. 4. Department of Animal Science, College of Agriculture, Shiraz University, Shiraz, 71441-65186, Iran
  5. 5. Department of Hematology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Chemosphere Published:2019


Abstract

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. © 2019 Elsevier Ltd