Mohammad Mehdi Ommati, Reza Heidari, Mohammad Javad Zamiri, Samira Sabouri, Ladan Zaker, Omid Farshad, Akram Jamshidzadeh, Saeed Mousapour
Biological trace element research 2020 MayExposure to arsenic (AS) causes abnormalities in the reproductive system; however, the precise cellular pathway of AS toxicity on steroidogenesis in developing F1-male mice has not been clearly defined. In this study, paternal mice were treated with arsenic trioxide (As2O3; 0, 0.2, 2, and 20 ppm in drinking water) from 5 weeks before mating until weaning and continued for male offspring from weaning until maturity (in vivo). Additionally, Leydig cells (LCs) were isolated from the testes of sacrificed F1-intact mature male mice and incubated with As2O3 (0, 1, 10, and 100 μM) for 48 h (in vitro). Biomarkers of mitochondrial impairment, oxidative stress, and several steroidogenic genes, including the steroidogenic acute regulatory (StAR) protein, cytochrome P450 side-chain cleaving enzyme (P450scc; Cyp11a), 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β-hydroxysteroid dehydrogenase (17β-HSD), were evaluated. High doses of As2O3 interrupted testosterone (T) biosynthesis and T-related gene expression in these experimental models. Altogether, overconsumption of As2O3 can cause testicular and LC toxicity through mitochondrial-related pathways and oxidative stress indices as well as downregulation of androgenic-related genes in mice and isolated LCs. These results could lead to the development of preventive/therapeutic procedures against As2O3-induced reproductive toxicity. Graphical Abstract Mohammad Mehdi Ommati and Reza Heidari contributed equally to this study.
Mohammad Mehdi Ommati, Reza Heidari, Mohammad Javad Zamiri, Samira Sabouri, Ladan Zaker, Omid Farshad, Akram Jamshidzadeh, Saeed Mousapour. The Footprints of Oxidative Stress and Mitochondrial Impairment in Arsenic Trioxide-Induced Testosterone Release Suppression in Pubertal and Mature F1-Male Balb/c Mice via the Downregulation of 3β-HSD, 17β-HSD, and CYP11a Expression. Biological trace element research. 2020 May;195(1):125-134
PMID: 31313246
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