Kaushal Naveen, Bansal M P
Department of Biophysics, Panjab University, Chandigarh 160 014, India.
J Biochem Mol Toxicol. 2009 Mar-Apr;23(2):125-36. doi: 10.1002/jbt.20276.
The oxidative stress imposed by nutritional variations in selenium (Se) has plausible role in reproductive toxicology and affects the reproductive potential. Also, the expression of heat shock proteins (HSPs) is a highly regulated event throughout the process of spermatogenesis and is modulated by stressful stimuli. This prompted us to investigate the possibility that Se-induced oxidative stress may affect the fertility status by altering the expressions of the constitutive and inducible HSP70 proteins, having crucial role in spermatogenesis. Different Se status-deficient, adequate, and excess, male Balb/c mice were created by feeding yeast-based Se-deficient diet (group I) and deficient diet supplemented with Se as sodium selenite at 0.2 and 1 ppm Se (group II and III) for a period of 8 weeks. After completion of the diet-feeding schedule, a significant decrease in the Se and glutathione peroxidase (GSH-Px) levels was observed in the Se-deficient group (I), whereas Se-excess group (III) demonstrated an increase. Increased levels of reactive oxygen species, malondialdehyde, and alterations in the redox status in both groups I and III indicated oxidative-stressed conditions. There was an overall reduced fertility status in mice supplemented with Se-deficient and Se-excess diet. The mRNA and protein expression of HSP70 was found to be elevated in these two groups, whereas the expression patterns of HSP70-2 and MSJ-1 demonstrated a reverse trend. In vitro CDC2 kinase assay showed reduced kinase activity in group I and group III. These findings suggest that Se-induced oxidative stress by differentially regulating various HSP70s can affect its downstream factors having crucially important role in differentiation of germ cells and completion of spermatogenesis. Therefore, it can provide an insight into the mechanism(s) by which the oxidative stress-induced reproductive toxicity can lead to increased apoptosis/growth arrest and infertility. This will thus add new dimensions to the molecular mechanism underlying the human male infertility and open new vistas in the development of various chemo-preventive methods.
硒（Se）营养变化所施加的氧化应激在生殖毒理学中可能发挥作用，并影响生殖潜能。此外，热休克蛋白（HSPs）的表达在精子发生过程中是一个高度受调控的事件，并受到应激刺激的调节。这促使我们研究硒诱导的氧化应激是否可能通过改变组成型和诱导型HSP70蛋白的表达来影响生育状况，而这些蛋白在精子发生中起着关键作用。通过给雄性Balb/c小鼠喂食基于酵母的缺硒饮食（第一组）以及补充了0.2 ppm和1 ppm硒亚硒酸钠的缺硒饮食（第二组和第三组）8周，创建了不同硒状态（缺乏、充足和过量）的小鼠。在完成饮食喂养计划后，缺硒组（第一组）的硒和谷胱甘肽过氧化物酶（GSH-Px）水平显著降低，而硒过量组（第三组）则有所升高。第一组和第三组中活性氧、丙二醛水平的升高以及氧化还原状态的改变表明存在氧化应激条件。喂食缺硒和硒过量饮食的小鼠总体生育状况降低。在这两组中发现HSP70的mRNA和蛋白表达升高，而HSP70-2和MSJ-1的表达模式则呈现相反趋势。体外CDC2激酶测定显示第一组和第三组的激酶活性降低。这些发现表明，硒诱导的氧化应激通过差异调节各种HSP70s可影响其在生殖细胞分化和精子发生完成中起至关重要作用的下游因子。因此，它可以深入了解氧化应激诱导的生殖毒性导致细胞凋亡/生长停滞增加和不育的机制。这将为人类男性不育的分子机制增添新的维度，并为各种化学预防方法的开发开辟新的前景。
