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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

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Abstract

Exposure 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.

Mohammad Mehdi Ommati and Reza Heidari contributed equally to this study.

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Funding

This study was supported by the Science and Technology Innovation Fund of Shanxi Agricultural University (2018YJ33) and the Pharmaceutical Sciences Research Center of Shiraz University of Medical Sciences, Shiraz, Iran (Grant No. 18842/17549).

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  1. Mohammad Mehdi Ommati and Reza Heidari contributed equally to this work.

Authors and Affiliations

  1. Department of Bioinformatics, College of Life Sciences, Shanxi Agricultural University, Taigu, 030801, Shanxi, People’s Republic of China

    Mohammad Mehdi Ommati & Samira Sabouri

  2. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Fars, 158371345, Iran

    Reza Heidari, Omid Farshad & Akram Jamshidzadeh

  3. Department of Animal Science, College of Agriculture, Shiraz University, Shiraz, Iran

    Mohammad Javad Zamiri

  4. Department of Hematology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Ladan Zaker

  5. Department of Embryo Technology Research Institute, Shahr-e Kord University, Shahr-e Kord, Iran

    Saeed Mousapour

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  1. Mohammad Mehdi Ommati
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Ommati, M.M., Heidari, R., Zamiri, M.J. et al. 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. Biol Trace Elem Res 195, 125–134 (2020). https://doi.org/10.1007/s12011-019-01815-2

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