Dysregulated apoptosis through the intrinsic pathway in the internal spermatic vein of patients with varicocele.
OBJECTIVE
Apoptosis plays a critical role in various physiological processes. Varicocele is the most common cause of male infertility in adults. The dilated and thickened wall of the internal spermatic vein (ISV) in varicocele is considered similar to that in varicose veins. We investigated apoptotic protein expression in the ISV of varicocele, including Bcl-2, Fas, caspase-8 and caspase-9, to determine the intrinsic or extrinsic pathway.


METHODS
The study group consisted of 10 patients with grade 3 left varicocele. The control group consisted of 10 patients with left indirect inguinal hernia. A 1-cm section of ISV was resected, using left inguinal incision, from each patient in both groups. The ISV sections were used to detect the mediators that regulate the intrinsic (Bcl-2 and caspase-9) and extrinsic (Fas and caspase-8) apoptotic pathways, by immunoblotting and immunohistochemical staining. Results were analyzed using Student's t tests.


RESULTS
Bcl-2, Fas, caspase-8 and caspase-9 immunoblots from both groups revealed a single band. The relative intensities of the Bcl-2 and caspase-9 protein bands differed significantly between the varicocele and control groups. Thickening of the smooth muscle layer of the ISV was found in patients with varicocele compared with the control group. Bcl-2 overexpression and downregulation of caspase-9 expression were noted in the varicocele group. There was no significant difference in Fas or caspase-8 expression in either group.


CONCLUSIONS
We showed overexpression of Bcl-2 and downregulation of caspase-9 expression in the ISV under hypoxic stress. This indicated dysregulated apoptosis through the intrinsic pathway in the ISV of patients with varicocele. To the best of our knowledge, this is the first study of the apoptotic pathway in the human ISV. Additional studies are needed to establish whether adjunctive hyperbaric oxygen therapy reduces the recurrence rate after varicocelectomy.
Lee
Jane-Dar
JD
Division of Urology, Department of Surgery, Armed Forces Taichung General Hospital, Taiwan.
Lu
Lieng-Yi
LY
Cheng
Wen-Hsuan
WH
Jeng
Shaw-Yeu
SY
D000328:Adult; D017209:Apoptosis; D053453:Caspase 9 / Q000378:metabolism; D006801:Humans; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013085:Spermatic Cord / Q000098:blood supply*; D014646:Varicocele / Q000473:pathology*
D019253:Proto-Oncogene Proteins c-bcl-2; D053453:Caspase 9