Experimental Varicocele Model Research Articles

EXPERIMENTAL VARICOCELE INDUCES HYPOXIA INDUCIBLE FACTOR-1α, VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION AND ANGIOGENESIS IN THE RAT TESTIS

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. 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. 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). 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.

The role of reactive oxygen species and apoptosis in the pathogenesis of varicocele in a rat model and efficiency of vitamin E treatment.

We investigated role of reactive oxygen species (ROS) and apoptosis in the pathogenesis of infertility in experimental model of varicocele. The protective effect of vitamin E was also examined. Three groups of rats were constructed as the first group had sham operation, experimental varicoceles were established by partial ligation of the left renal vein in later two groups. Third group had received vitamin E. Production of ROS was determined by chemiluminescence assay (CL). The in situ end labelling technique was utilized to investigate apoptosis. Tissue vitamin E levels were measured by high performance liquid chromatography. The differences between luminol enhanced CL levels of groups were not statistically significant. However, the difference between CL levels of lucigenin probe in left testicles of sham and varicocele groups were statistically significant ( p = 0.0007). Similarly, the results of the third group receiving vitamin E significantly differed from the varicocele group ( p = 0.0025). The difference of apoptotic index was also statistically significant between sham and varicocele groups ( p = 0.0038). Although the values of apoptotic index detected in the vitamin E group were lower compared with the varicocele group, the difference was not significant. This study proposes that ROS production and apoptosis in the testicles were induced with experimental varicocele. Vitamin E had a protective role. An increased rate of apoptosis with experimental varicocele suggests a molecular alteration, which may involve ROS overproduction as the triggering mechanism. Consequently, this study indicates an association between varicocele and infertility at molecular level through stimulation of ROS and apoptosis.

The venous anatomy of experimental left varicocele: comparison with naturally occurring left varicocele in the human

To determine the effect of experimental left varicocele on the anatomy of the veins serving the rat testis and to compare that anatomy to known patterns of vascular drainage from the human testis with and without varicocele. Vascular maps were made of the effluent vessels from the rat testis in control animals and those with a 30-day experimental left varicocele. Consensus maps were arrived at and these were compared to published reports of the pertinent venous anatomy in humans with and without varicocele. Research laboratory. The major route of blood leaving the rat testis was confirmed to be the spermatic vein, but nine common collaterals were also found to exist. Four of these collaterals became more pronounced with experimental varicocele as did several dilated perineal veins. These latter vessels all led to the iliac vein. The vasculature of the rat experimental varicocele model shares some important anatomical features with human varicocele anatomy. Varicocele in humans and in the rat model causes a redistribution of blood flow from a route primarily out the spermatic vein to routes leading to the iliac vein. The redistribution is similar but not identical.

Surgical repair of secondary right varicocele in rats with primary left varicocele: effects on fertility, testicular temperature, spermatogenesis, and sperm maturation.

To evaluate whether or not dilation of the right testicular vein is a constant finding in animals with left varicocele and to illustrate its contribution to the detrimental effect of a left varicocele on the right testis, an experimental varicocele model was produced in 40 rats. Ten other rats had a sham operation (group A). Seven weeks after the operation, all 50 rats underwent laparotomy and dilation of both testicular veins was seen in 23 rats, which were randomly assigned to group B (n = 11) and group C (n = 12). One week later, groups A and C underwent sham ligation of the right testicular vein, whereas group B rats underwent resection of this vein. At 84 days after the initial operation, group C rats showed a significant reduction in right epididymal sperm content, motility, and fertilizing capacity, right testicular weight, and right testicular vs. intraabdominal temperature difference when compared with groups A and B. Since surgical repair of the secondary right varicocele improved all the parameters indicating the harmful consequences of the primary left varicocele on the right testis, it appears that dilation of the right testicular vein contributes to the detrimental effect of a left varicocele on the right testis.

Autoimmune nature of the disturbance of spermatogenesis in rats with experimental varicocele

Measured disturbance of the venous outflow from the left testis in rats causes the development of destructive changes in the spermatogenic epithelium both in the testis on the side of the operation and also in the contralateral organ. Disturbances of spermatogenesis in rat testes (foci of desquamation of spermatogenic epithelium, disorganization and degeneration of the sex cells, emptying of the seminiferous tubules) are similar to those in men with varicocele, so that the results of such experiments can be regarded as an experimental model of varicocele. In the experimental rats the permeability and fine structure of the blood-testis barrier were disturbed in both testes, the pattern of the morphological changes was similar with that observed during the development of autoimmune orchitis, and lymphocytes sensitized to spermatozoal antigens were found in the lymphoid organs. Taken as a whole, the results suggest involvement of immunologic mechanisms in the development of the pathological changes in the testes in varicocele.