Diethyl Maleate-Induced Oxidative Stress Leads to Testicular Germ Cell Apoptosis Involving Bax and Bcl-2

Testicular germ cell apoptosis is normally a continuous process throughout life. However, massive testicular germ cell loss is known to result from a wide variety of cellular stresses including toxicant exposure. Thus, the present study was aimed to investigate the mechanisms of germ cell loss under stress conditions following diethyl maleate (DEM) exposure. Stress conditions were generated in male Balb/c mice by depleting glutathione by DEM administration. The germ cell apoptosis was found to be increased as assessed by terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-UTP biotin nick end labeling (TUNEL) staining, evaluation of histoarchitechture of testis, and germ cell numbers. It was found that the germ cell number was significantly reduced in DEM-treated sections. RT-PCR was carried out to assess Bax/Bcl-2 mRNA expression levels. Immunohistochemistry of Bax and Bcl-2 revealed Bax activation. The prevalence and cellular localization of the above markers in testicular tissues of DEM-treated animals suggest the possible involvement of Bax/Bcl-2 in the male germ cell apoptosis. (C) 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:371-381, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10:1002/jbt.20252