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.
Mohammad Mehdi OmmatiReza HeidariMohammad Javad ZamiriSamira SabouriLadan ZakerOmid FarshadAkram JamshidzadehSaeed MousapourPublished in: Biological trace element research (2019)
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. Graphical Abstract Mohammad Mehdi Ommati and Reza Heidari contributed equally to this study.
Keyphrases
- oxidative stress
- drinking water
- diabetic rats
- induced apoptosis
- gene expression
- dna damage
- ischemia reperfusion injury
- high fat diet induced
- drug induced
- cell proliferation
- heavy metals
- health risk
- health risk assessment
- signaling pathway
- dna methylation
- mechanical ventilation
- liver failure
- high glucose
- poor prognosis
- type diabetes
- high fat diet
- wild type
- intensive care unit
- mass spectrometry
- hepatitis b virus
- extracorporeal membrane oxygenation
- newly diagnosed
- cell death
- insulin resistance
- adipose tissue
- replacement therapy
- long non coding rna
- amino acid
- bioinformatics analysis
- simultaneous determination
- cell cycle arrest
- protein protein