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Transgenic Rodent Assay for Quantifying Male Germ Cell Mutant Frequency
Published on: August 6, 2014
Dietary selenium variation-induced oxidative stress modulates CDC2/cyclin B1 expression and apoptosis of germ cells
Naveen Kaushal1, Mohinder P Bansal
1Department of Biophysics, Panjab University, Chandigarh 160014, India.
Abstract:
Oxidative stress has been linked with apoptosis in germ cells and with male infertility. However, the molecular mechanism of oxidative-stress-mediated apoptosis in germ cells has not been clearly defined so far. Because of the involvement of CDC2 and cyclin B1 in cell cycle regulation and their plausible role in apoptosis, the present study aimed to investigate the possibility that selenium (Se)-induced oxidative-stress-mediated modulations of these cell cycle regulators cause DNA damage and apoptosis in germ cells. To create different Se status (deficient, adequate and excess), male Balb/c mice were fed yeast-based Se-deficient diet (Group I) and a deficient diet supplemented with Se as sodium selenite (0.2 and 1 ppm Se in Groups II and III, respectively) for a period of 8 weeks. After the completion of the diet feeding schedule, a significant decrease in Se levels and glutathione peroxidase activity was observed in the Se-deficient group (Group I), whereas the Se-excess group (Group III) demonstrated an increase in Se levels. Increased levels of lipid peroxidation were seen in both Groups I and III when compared to Group II, indicating oxidative stress. The mRNA and protein expressions of both CDC2 and cyclin B1 were found to be significantly decreased in Groups I and III. A decrease in the immunohistochemical localization of these proteins was also observed in spermatogenic cells. The mRNA expressions of apoptotic factors such as Bcl-2, Bax, caspase-3 and caspase-9 were found to be increased in Groups I and III. A decrease in CDC2 kinase activity was also seen in these groups. Increased apoptosis was observed in Group I and Group III animals by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling assay indicating oxidative-stress-mediated DNA damage. These findings suggest the effect of Se-induced oxidative stress on the cell cycle regulators and apoptotic activity of germ cells, thus providing new dimensions to molecular mechanisms underlying male infertility.
Insights
Selenium (Se) status impacts germ cell apoptosis and male infertility. Both Se deficiency and excess induce oxidative stress, altering cell cycle regulators (CDC2, cyclin B1) and increasing germ cell DNA damage and apoptosis.
Area of Science:
- Reproductive Biology
- Toxicology
- Cell Biology
Background:
- Oxidative stress is implicated in germ cell apoptosis and male infertility.
- The precise molecular mechanisms of oxidative-stress-induced germ cell apoptosis remain unclear.
Purpose of the Study:
- To investigate if selenium (Se)-induced oxidative stress modulates cell cycle regulators CDC2 and cyclin B1, leading to DNA damage and apoptosis in germ cells.
- To explore the role of Se status in male reproductive health.
Main Methods:
- Male Balb/c mice were fed Se-deficient, adequate, or excess diets for 8 weeks.
- Assessed Se levels, glutathione peroxidase activity, and lipid peroxidation.
- Analyzed mRNA and protein expression of CDC2, cyclin B1, and apoptotic factors (Bcl-2, Bax, caspase-3, caspase-9).
- Evaluated CDC2 kinase activity and germ cell apoptosis via TUNEL assay.
Main Results:
- Se deficiency and excess increased lipid peroxidation, indicating oxidative stress.
- Both Se deficiency and excess significantly decreased CDC2 and cyclin B1 mRNA and protein expression and CDC2 kinase activity.
- Apoptotic factors increased, and germ cell apoptosis was elevated in Se-deficient and Se-excess groups.
- DNA damage was observed in germ cells of Se-deficient and Se-excess mice.
Conclusions:
- Selenium-induced oxidative stress affects germ cell cycle regulators and apoptotic pathways.
- Modulation of CDC2 and cyclin B1 by oxidative stress contributes to DNA damage and apoptosis in germ cells.
- These findings offer insights into the molecular mechanisms of male infertility linked to Se status.
