Cadmium chloride rapidly alters both BTB tight junction proteins and germ cells in young rat testes

Abstract

Intraperitoneal injections (ip) of cadmium chloride (CdCl 2) cause a marked and prolonged reduction of spermatogenesis, accompanied by increased permeability of the blood-testis barrier. Because the permeability of the blood-testis barrier is regulated by Sertoli cell tight junctions, and tight junction organization is regulated by the cytoskeleton, we undertook to examine the effects of CdCl 2 treatment on intermediate filaments vemintin, and on the tight junction protein, occludin, adherens junction N-Cadhern and gap junction connexin 43 in seminiferous tubules. Three weeks old rats received (ip) low or high dose (1 mg or 2 mg/kg body weight) of either CdCl 2 solution or saline (control) for 6 days. After injection, testes were collected and prepared for routine histology or whole seminiferous tubule Immunocytochemistry staining, and the preparations were viewed by light and electron microscopy for histopathology and fluorescence microscope for Immunocytochemistry studies. The results indicate that cadmium exposure induces different degrees of histopathological alterations with both light and electron microscopy. Also, tight junction proteins occludin, N-cadherin and vimentin are all partially or completely disrupted by a cadmium injection. These results are consistent with cadmium-induced damage to rat testis as well as to tight junctions between adjacent intact cells. Perturbation of the tight junction-associated proteins could explain the increase in permeability of the blood-testis barrier observed after CdCl 2 treatment. Impaired spermatogenesis following CdCl 2 treatment is likely a consequence of a leaky blood testis barrier and disrupted Sertoli cell cytoskeleton. CdCl 2 injections may serve as a useful tool in studying the relationship between cytoskeletal organization and the stabilization of Sertoli-Sertoli cell junctions. Suggesting that damage to Sertoli cell tight junctions induced by cadmium may be an underlying mechanism of their male-mediated reproductive toxicity.