Non-Communicable Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Surgery, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
J Reprod Immunol. 2020 Aug;140:103131. doi: 10.1016/j.jri.2020.103131. Epub 2020 Apr 18.
An enlargement of the spermatic vein is known as a varicocele. Research studies suggest that immune system mediators such as vascular endothelial growth factor (VEGF) and its receptors including VEGFR1, VEGFR2, and VEGFR3 can play a role in angiogenesis and inhibition of endothelial cell apoptosis and correspondingly suppress spermatogenesis. Thus, the purpose of this study was to measure the expression of VEGF and its receptors in infertile men with varicocele.
MATERIALS & METHODS: To meet the research objectives, a total number of 30 infertile male patients affected with varicocele (Grade 3) and 30 healthy fertile male subjects without any varicocele or urogenital tract disorder were enrolled in the study. The varicose and normal veins were obtained from the patients along with the blood flowing in these spermatic veins during surgery. Also, peripheral blood samples were collected from the mentioned patients and healthy subjects. The serum levels of VEGF were also measured via enzyme-linked immunosorbent assay (ELISA) and subsequently mRNA level of VEGFR1, VEGFR2, VEGFR3, B Cell Lymphoma-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes were measured using the real-time polymerase chain reaction (RT-PCR) technique.
The findings of this study revealed that VEGFR2 gene expression in varicose veins was significantly increased compared with normal veins in varicocele patients (P < 0.001) and Bax/Bcl2 ratio reduced in varicose veins when compared to normal veins of the patients (P < 0.05). Our findings also showed a significant rise in the serum levels of VEGF in the peripheral blood and varicose vein bloodstream compared with those in healthy subjects (P < 0.0001). Moreover, a significant difference was observed in the serum levels of VEGF in the peripheral blood and varicose vein blood of patients suffering from varicocele (P < 0.001).
According to the results of this study, VEGF/VEGFR2 axis might act in the survival of endothelial cells of varicocele vein through inhibition of apoptosis and stimulation of angiogenesis. Additionally, increased VEGF in the testis can probably play a role in suppressing spermatogenesis and varicocele-based infertility.
精索静脉曲张是指精索静脉的扩张。研究表明，免疫系统介质如血管内皮生长因子（VEGF）及其受体，包括 VEGFR1、VEGFR2 和 VEGFR3，可以在血管生成和抑制内皮细胞凋亡中发挥作用，并相应地抑制精子发生。因此，本研究的目的是测量精索静脉曲张患者中 VEGF 及其受体的表达。
为了达到研究目的，共招募了 30 名患有精索静脉曲张（3 级）的不育男性患者和 30 名无精索静脉曲张或泌尿生殖道疾病的健康生育男性作为对照。在手术过程中，从患者的精索静脉曲张和正常静脉中采集静脉血。此外，还从上述患者和健康受试者中采集外周血样本。通过酶联免疫吸附试验（ELISA）测量血清 VEGF 水平，并用实时聚合酶链反应（RT-PCR）技术测量 VEGFR1、VEGFR2、VEGFR3、B 细胞淋巴瘤相关 X（Bax）和 B 细胞淋巴瘤 2（Bcl2）基因的 mRNA 水平。
本研究结果表明，与精索静脉曲张患者的正常静脉相比，静脉曲张患者的静脉中 VEGFR2 基因表达显著增加（P < 0.001），并且 Bax/Bcl2 比值在静脉曲张时降低与患者的正常静脉相比（P < 0.05）。我们的研究结果还表明，与健康受试者相比，外周血和精索静脉曲张血流中的 VEGF 血清水平显著升高（P < 0.0001）。此外，精索静脉曲张患者外周血和精索静脉曲张血中 VEGF 的血清水平存在显著差异（P < 0.001）。
根据本研究的结果，VEGF/VEGFR2 轴可能通过抑制凋亡和刺激血管生成来维持精索静脉曲张静脉内皮细胞的存活。此外，睾丸中 VEGF 的增加可能在抑制精子发生和精索静脉曲张相关不育中起作用。
