title: Hypoxia-induced apoptosis in the bilateral testes of rats with left-sided varicocele: a new way to think about the varicocele.
abstract: 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.
authors.affiliation: Urology Department of Changhai Hospital, Changhai Road 174#, Yangpu District, Shanghai, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.forename: Linhui
authors.initials: L
authors.lastname: Wang
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D005854:Germ Cells / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007248:Infertility, Male / Q000209:etiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000098:blood supply / Q000473:pathology; D014646:Varicocele / Q000150:complications / Q000503:physiopathology*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit