Experimental varicocele induces hypoxia inducible factor-1alpha, vascular endothelial growth factor expression and angiogenesis in the rat testis

PURPOSE: In this study we investigated hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression, and angiogenesis in an experimental model of varicocele in the rat testis. MATERIALS AND METHODS: A total of 30 adult male Sprague-Dawley rats were investigated in 3 groups, namely varicocele group 1 (13), sham operated group 2 (9) and control group 3 (8). At 30 days after surgery was completed in groups 1 and 2 orchiectomy was performed in all rats. Histological findings in the left testicles of rats from each group were compared. HIF-1alpha and VEGF expression was immunohistochemically studied and CD31 panendothelial antigen was used to identify the number of microvessels, that is microvessel density (MVD), in paraffin embedded sections of testis tissue. Data were analyzed using the chi-square test, Fisher's exact test, 1-way ANOVA and the Tukey HSD test for post hoc comparison. RESULTS: HIF-1alpha expression was detected in 12 specimens (92.3%) in group 1, 4 (44.4%) in group 2 and 2 (25%) in group 3. The frequency of HIF-1alpha positivity in group 1 was significantly higher than the rates in groups 2 (p = 0.023) and 3 (p = 0.003). VEGF expression was detected in 8 specimens (61.5%) in group 1 but none of the group 2 or 3 specimens were VEGF positive. The frequency of VEGF positivity in group 1 was significantly higher than that in groups 2 (p = 0.006) and 3 (p = 0.007). Mean MVD +/- SD in group 1 was 7.53 +/- 1.50 (range 6 to 12), and findings in groups 2 and 3 were 5.88+/-1.45 (range 4 to 8) and 5.12 +/-1.12 (range 4 to 7), respectively. Mean MVD in group 2 was higher than in group 3 but this difference was not significant (p = 0.509). Mean MVD in group 1 was significantly higher than the mean values in groups 2 (p = 0.030) and 3 (p = 0.002). CONCLUSIONS: Previous study of experimental varicocele models in rats documented HIF-1alpha and VEGF expression combined with angiogenesis in the testis. The results of this study show that varicocele can lead to tissue hypoxia and related pathophysiological events, such as angiogenesis.