Alterations in selenium status influences reproductive potential of male mice by modulation of transcription factor NFkappaB.

Selenium (Se), an essential dietary trace element, is required for the maintenance of male fertility. In order to study its role in spermatogenesis, Balb/c mice with different Se status (Se deficient, group I; adequate, group II and excess, group III) were generated by feeding yeast based Se deficient diet for group I and deficient diet supplemented with Se as sodium selenite at adequate (0.2 ppm) and excess (1 ppm) for group II and III, respectively, for a period of 4 and 8 weeks. Percentage fertility was reduced in group I and III as compared to group II. A significant decrease in Se levels and glutathione peroxidase (GSH-Px) activity were observed in group I animals, whereas increase in GSH-Px activity was seen in group III. Further, significant increase in lipid peroxidation was observed in both Se deficient and excess groups. This indicated that dietary manipulation of Se levels either deficiency or excess leads to increased oxidative stress. Nuclear factor kappa B (NFkappaB), a well-known redox regulated transcription factor has also been suggested to play a crucial role in spermatogenesis. The expression of both p65 and p50 genes (components of NFkappaB) increased in Se deficient group I mice while the expression of the inhibitory IkappaBalpha declined significantly. This indicated activation of NFkappaB in Se deficiency. We also studied iNOS expression, which is a known target gene of NFkappaB, by RT-PCR. Significant elevation in the iNOS levels as well as NO levels was recorded. Both enhanced NO levels and NFkappaB are harmful in the progression of normal spermatogenic cycle. Therefore, present result clearly demonstrates the effect of reduced supply of Se on up-regulation and activation of NFkappaB in testis and its influence on spermatogenesis.