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Delineating the Molecular Mechanism behind Regulation of Spermatogenesis by Selenium: Involvement of Mitogen Activated Protein Kinase; JNK

Department of Biophysics, Panjab University, Chandigarh, India

*Corresponding Author:

M.P. Bansal

Department of Biophysics

Panjab University,

Chandigarh160014, India

E mail: mpbansal@pu.ac.in

Tel: 0172-2534120

Fax: 0172-2534118

Abstract

Selenium is required for maintenance of male fertility. It regulates cell growth, cytotoxicity and transformation. Previous studies from our lab demonstrated inactivation of transcription factor AP-1 by selenium status. Nonetheless, the modulatory functions of selenium and other selenium compounds on intracellular signaling pathways involving the MAPKs are not fully understood. The mitogen- activated protein kinase (MAPK) pathway is one of the most widely studied signaling pathways involved in the transduction of intracellular signals initiated by extracellular stimuli to the nucleus. Amongst MAPKs, the c-jun N- terminal kinase (JNK MAPK) is an upstream kinase for transcription factor, Activator protein (AP-1). AP-1 plays a role in cell proliferation and transformation; and is sensitive to oxidants, anti-oxidants and conditions which affect the cellular redox state. In this respect, the upstream kinase for AP-1, JNK MAPK, might also be sensitive to the selenium status. Thus, to delineate the molecular pathway involved in the selenium action as a regulator of spermatogenesis, the upstream kinase for AP-1, the JNK MAPK was explored further under selenium stress conditions. Different selenium status-deficient, adequate and excess selenium were generated in male mice by feeding respective diets for a period of 4 and 8 weeks. Selenium status and GSH-Px activity was checked in testis. The reproductive potential of mice was affected at these altered selenium levels. There was a decrease in the SOD activity and reduced glutathione levels concomitant with an increase in the oxidized glutathione levels, indicative of oxidative stress. mRNA expression of GSH-Px, MnSOD and γGCS was found to be altered. There was an increase in the mRNA and protein expression of JNK MAPK which was further confirmed by its immunohiostochemical localization studies. Thus, the study clearly shows that JNK MAPK, an upstream kinase for AP-1 regulates spermatogenesis independently of AP-1. The decrease in reproductive potential as observed in the present study might result from the alteration in the redox environment of the testicular compartment.

Keywords:  Selenium; AP-1; JNK MAPK; spermatogenesis; male fertility.

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