Disruption of Leydig cell steroidogenic function by sodium arsenite and/or sodium fluoride

Many of the compounds found in natural sources have harmful effects besides beneficial effects on living organisms. Although As and F, which are commonly found in water and food, are necessary for the environment and human health, high concentrations are known to have potentially harmful effects. Due to their daily diet and drinking water, it is inevitable for humans to be exposed to compounds found in abundance in nature, such as As and F. Various daily intake limits are set for such compounds with toxic effects, and these limits are determined as 10 ppb for As and 1.5 ppm for F [1,2]. Many developed or developing countries such as United States, Africa, Asia, China, India, and Turkey, has endemic areas containing As and F [[1], [2], [3]]. Therefore, it is of great importance to examine the toxic effects of As and F separately and together. F is found in a wide range, including water, air, food, pharmaceuticals, cosmetics, and industry. As is found in high concentrations at groundwater, and it is entered into the body via contaminated nutrients as it is used as an insecticide [4]. The rapid ionization of F and As in water accelerates the passage to the cells and their toxic effects increase due to the formation of compounds with the cations present in the cell.

The accumulation of As and F in the body causes a variety of disorders, including hematological, neurological, renal and hepatic issues, according to several clinical research and animal trials [5]. F and As can affect cells from protein damage to the formation of free radicals. As a result, it was observed that cell function impairment and apoptotic cell death increased [6,7]. F and/or As stimulates genotoxicity induced by free radical formation in various cell lines and increases lipid peroxidation [8]. F and As exposure have a particularly detrimental effect on the reproductive system. Physiological effects of F and As have been revealed in many clinical and laboratory studies, and in animal species tested the toxicity of these compounds has been shown to result in infertility [9,10]. Studies have shown that F and/or As negatively affect key processes for fertilization such as, sperm morphology and motility, capacitation and acrosome reaction [11,12]. Various reproductive hormones, such as testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), are essential for testicular androgenesis and proper spermatogenesis. F and As damages many hormones involved in the male reproductive system. Studies have revealed the effects of F on increased FSH and LH, decreased estrogen, testosterone and thyroid hormone levels, unbalanced androgen/estrogen ratio [[13], [14], [15]]. These endocrine disrupting effects of F and As cause decreased reproductive capacity. Although studies investigating the effect of F and As on spermatozoa and male infertility have increased in the last years [10,16,17], there is a lack of information on which pathway that shows its effects on the male reproductive system.

Leydig cells are the main cells that produce testosterone necessary for the completion of sexual differentiation and reproductive functions in men. Chronic stimulation of Leydig cells by LH or cyclic adenosine monophosphate requires optimal expression of the enzymes necessary for the biosynthesis of testosterone from cholesterol. Among the enzymes involved in Leydig cell steroidogenesis are cytochrome P450 Family 11 Subfamily A Member 1 (CYP11A1), cytochrome P450 Family 17 Subfamily A Member 1 (CYP17A1), steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). In this context, Leydig cells were used in the study as an in vitro model to demonstrate the toxicity of F and/or As. In this study, the effects of As and F separately and together on Leydig cell function and testosterone biosynthesis were investigated by measuring cell cytotoxicity, antioxidant/oxidant balance, apoptosis rate, testosterone levels, expression level of steroidogenic genes such as StAR, Cyp11a1, Hsd3b1, Hsd17b3 and activity of steroidogenic enzymes including 3β-HSD, 17β-HSD.

留言 (0)

沒有登入
gif