Lindane induces testicular apoptosis in adult Wistar rats through the involvement of Fas-FasL and mitochondria-dependent pathways

Lindane, an organochlorine pesticide, is known to impair testicular functions and fertility. To elucidate the mechanism(s) underpinning the gonadal effects of lindane, we sought to investigate the levels of apoptosis-related proteins, namely cytochrome c, caspase-3 and -9, Fas and FasL. in the testis of adult rats. Furthermore, the study aims to delineate whether nuclear factor kappa B (NF-kappa B) is involved in meditating the testicular effects of lindane. Animals were administered with a single dose of lindane (5 mg/kg body weight) and sacrificed at specific post-treatment intervals (0, 3, 6, 12. 24 and 72 h). Significant elevations in the levels of cytosolic cytochrome c with a parallel increase in pro-caspase-9 were observed Time-dependent elevations in the levels of Fas, FasL and caspase-3 as 6 h following exposure as early were observed. Immunofluorescence studies revealed increased colocalization of Fas and caspase-3 in peritubular germ cells. FasL. levels were increased in Sertoli and peritubular germ cells. The cytoplasmic levels of NF-kappa B p65 decreased from 3 h following exposure with a maximal decline at 12 and 24 h. Changes in the localization of NF-kappa B were observed with maximal nuclear translocation in germ cells at 12 and 24 h. Terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) assay revealed a time-dependent increase in the number of apoptotic cells. Taken together, the data illustrate induction of testicular apoptosis in adult rats following exposure to a single dose of lindane. Early activation of NF-kappa B in contrast to late increase in Fas expression suggests a pro-apoptotic role of NF-kappa B in testicular response to lindane. (C) 2008 Elsevier Ireland Ltd. All rights reserved.