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-kappaB) is involved in meditating the testicular effects of
lindane. Animals were administered with a single dose of
lindane (5mg/kg
body weight) and sacrificed at specific post-treatment intervals (0, 3, 6, 12, 24 and 72h). Significant elevations in the levels of cytosolic
cytochrome c with a parallel increase in
pro-caspase-9 were observed as early as 6h following exposure. Time-dependent elevations in the levels of Fas, FasL and
caspase-3 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-kappaB p65 decreased from 3h following exposure with a maximal decline at 12 and 24h. Changes in the localization of
NF-kappaB were observed with maximal nuclear translocation in germ cells at 12 and 24h.
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-kappaB in contrast to late increase in Fas expression suggests a pro-apoptotic role of
NF-kappaB in testicular response to
lindane.