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-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.
Saradha
B
B
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry 605 014, India.
Vaithinathan
S
S
Mathur
P P
PP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053222:Fas Ligand Protein / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; D007306:Insecticides; D016328:NF-kappa B; D019014:fas Receptor; D001556:Hexachlorocyclohexane; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9