Abstract: 64

CADMIUM UPREGULATES VASCULAR PERMEABILITY FACTOR (VPF) EXPRESSION IN LEYDIG CELLS AND SERTOLI CELLS.

CL Au^{1 *}, CC Sy¹ , LF Chan¹ , WM Lee²
Department of Physiology, Chinese University of Hong Kong, Shatin, Hong Kong ¹
Department of Zoology, University of Hong Kong, Hong Kong ²

Cadmium (Cd)-induced testicular toxicity is associated with a marked increase in the permeability of testicular blood vessels. The possible involvement of VPF in this process was examined in the present study based on Northern blot analysis of changes in VPF mRNA levels in testicular cells/tissues following in vitro or in vivo exposure to cadmium chloride (CdCl₂). Cultured mouse Leydig (TM3) and Sertoli (TM4) cell lines were used together with adult SD rats. Total RNAs extracted from cell lysates or tissues were fractionated on 1% agarose gel and transferred to Hybond-N⁺ membrane for hybridization with a ³²P-labelled VEGF cDNA probe. The hybridization signals were quantified using a phosphor imaging system and corrected for loading differences based on -actin. Comparisons were made against corresponding time controls and statistical significance of densitometric data was determined using one-way ANOVA. Results indicated that CdCl₂ induced a time- and concentration-dependent upregulation of VPF expression in TM3 and TM4 cells with the maximum responses (P<0.05) occurring at 6 h and with a dose of 30 µM. In adult rats, 6 mg/kg bw CdCl₂ produced a 2.5 fold (P<0.05) stimulation of VPF mRNA levels in the testes at 12 h after a single i.p. injection. Prior treatment of adult rats with ethane dimethane sulfonate (75 mg/kg bw) to selectively destroy the Leydig cells led to about 40% reduction in the basal and Cd-stimulated expression of VPF in the testes. The present data provide circumstantial evidence to suggest that upregulation of VPF expression could be responsible for the Cd-induced vascular permeability increase in the testis, and this is also in line with the fact that such permeability changes can occur even in the absence of Leydig cells. Supported by RGC Grants CUHK422/95M and CUHK 4270/97M.

    This abstract is being presented on Sunday, August 1 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.