metallothionein and Varicocele

The increased blood stasis and venous volume pressure causing tissue hypoxia are observed in both varicocele and varicose veins. Metallothionein (MT), a metal-binding protein, protects against cell apoptosis under hypoxic stress. It also plays an important role in collateral flow recovery and angiogenesis. We studied the distribution of hypoxia-inducible factor-1α (HIF-1α) and MT in varicocele and varicose veins.. The study specimens consisted of 1 cm venous segments that were obtained from 12 male patients during vascular stripping surgery for varicose veins and 1 cm of internal spermatic vein (ISV) obtained from 12 patients during left varicocele repair. The control samples of 1 cm ISV were obtained from 10 male patients who underwent left inguinal herniorrhaphy. All vascular specimens were analysed for HIF-1α and MT expression by immunoblotting, immunohistochemical (IHC) staining and confocal microscopy. Data were analysed using one-way analysis of variance with Tukey's comparison test.. In both venous diseases, the increased expression of HIF-1α and MT compared with the control group (P < 0.05) and most of the proteins distributed over smooth muscle layers were detected by IHC staining; HIF-1α and MT in the muscle layer with co-localization, and MT overexpression especially located in the endothelium of both venous diseases under confocal microscopy.. Our results revealed the higher expression of HIF-1α and MT in varicocele and varicose veins than in the control group; MT overexpression in the muscle layer of both diseased vessels and especially located in the endothelium under confocal microscopy. MT has the function to protect vascular cells from apoptosis under hypoxia. Thus, this MT function may cause a decreased vascular cell apoptosis and then contribute to the dilated and thickened walls of varicocele and varicose veins.

Topics: Adult; Apoptosis; Endothelium, Vascular; Female; Gene Expression Regulation; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Metallothionein; Middle Aged; Muscle, Smooth, Vascular; Stress, Physiological; Varicocele; Varicose Veins

To determine the possible molecular mechanism for the thickened wall in the internal spermatic vein (ISV) of patients with varicocele, we examined the cadmium (Cd) content and metallothionein (MT) expression in these diseased vessels. Previous studies have shown that Cd might play a role in the etiology of varicocele-associated infertility. MT, a metal-binding protein, protects against cell apoptosis during hypoxia.. The study group consisted of 20 patients with grade 3 left varicocele. The control group consisted of 15 volunteers with left-sided indirect inguinal hernia. Through a left inguinal incision, a 1-cm section of the ISV was resected from each patient to measure the Cd and MT levels. The results were analyzed using Student's t test.. The Cd content in the ISV was 59.84 +/- 5.7 ng/g in the control group and 192.1 +/- 24.2 ng/g in the varicocele group. The relative intensity of the MT band was 40.52 +/- 3.74 in the control group and 78.26 +/- 5.61 in the varicocele group. MT expression was greater in the varicocele group than in the control group, and its deposition in the vascular endothelial layer was predominant using immunohistochemistry staining and confocal laser scanning.. The results of the present study have demonstrated a greater accumulation of Cd in the ISV of the varicocele group than in the control group. The high Cd content and hypoxic conditions would induce overexpression of MT in the diseased vessels to protect the vascular cells from apoptosis. This might be a mechanism for the thickened wall of the ISV in patients with varicocele.

Topics: Cadmium; Humans; Male; Metallothionein; Testis; Varicocele; Veins; Young Adult