Modulatory effects of Selenium on Spermatogenesis: Involvement of transcription factors CREB and CREM

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In the testicular compartment, cAMP response element binding protein (CREB) and cAMP response element modulator (CREM) transcription factors are important transducers of hormonal signals into the induction of gene expression. Selenium (Se) is essential for male fertility. It has been shown earlier in our lab that selenite modulates Nuclear Factor κB, Activator Protein-1 and Stress Activated Protein Kinase pathways in the testicular mileau. Keeping all these in view, the present study was designed to explore further the intracellular pathways involved in spermatogenesis, by analyzing the transcription factors, CREB and CREM under Se status conditions. Also, the levels of Leutinising hormone, Follicle stimulating hormone and Testosterone were monitored to gain insight into the hormonal circuitry involved in the process. Mice were fed yeast based Se deficient, adequate and excess diet for 8 weeks after which they were sacrificed for further analysis. It was seen that Se deficient diet fed animals showed a reduction in testicular Se content alongwith decrease in glutathione peroxidase (GSH-Px) activity. On the other hand Se levels and GSH-Px activity increased in Se excess diet fed group. There was a significant decrease in the mRNA and protein expression of CREB and CREM after Se deficient and excess diet feeding. Also, there was a decrease in the levels of serum Testosterone, LH and FSH alongwith altered testicular histoarchitecture. Thus, spermatogenesis is altered by alteration in Se status. The altered Se status lead to changes in the levels of steroid hormones and the testicular circuitry was hampered. This lead to changes in the basal transcription machinery as demonstrated previously and in addition, the transcription factor CREB and CREM also showed changes in their expression. Thus, the study lead to a conclusion that spermatogenesis is a developmentally regulated program, and is under the control of complex hormonal circuitary which leads to modulation in the various signaling pathways governing cell survival and apoptosis depending upon the physiological conditions.