Hypoxia-Induced Apoptosis in the Bilateral Testes of Rats With Left-Sided Varicocele: A New Way to Think About the Varicocele

Although the varicocele has been studied for many years, its pathophysiology remains unclear. In this study, we investigated the expression of the alpha subunit of hypoxia-inducible factor 1 (HIF-1 alpha) and determined the apoptosis index (AI) in the testes of rats with varicoceles to study the mechanism by which varicoceles induce infertility. A total of 45 Wistar rats were divided into 3 groups: control group, sham surgery group, and experimental group. Forty-nine days after the initial partial ligation of the left renal vein, all of the rats underwent orchiectomy. HIF-1 alpha expression in each testis was analyzed using immunohistochemical methods and enzyme-linked immunosorbent assay. The degree of apoptosis within each testicle was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. HIF-1 alpha immunoreactivity in the testes of the experimental group was significantly higher than that in those of the control group (P < .05) or the sham group (P < .05). The AI of the germ cells of rats in the experimental group was significantly higher than that in germ cells of rats in the sham group (P < .001) or the control group (P < .001). Additionally, there was a significant positive correlation observed between the AI of germ cells and relative intensity of HIF-1 alpha in the left testis (r = .631; P = .028) and right testis (r = .707; P = .01) of rats in the experimental group. The results of this study showed that a left-sided varicocele could cause bilateral testicular hypoxia and increased germ cell apoptosis, both of which play an important role in testicular dysfunction. Furthermore, HIF-1 alpha is a useful factor that can be used to predict the degree of germ cell apoptosis in rat testes.