Effects Of Icariin On The Epididymal Lesions Of Varicocele-induced Rats

Background and objectives:Varicocele is characterized by abnormal tortuosity and dilation of the veins of the pampiniform plexus within the spermatic cord and is the most common cause of male infertility. The prevalence of varicocele in the general population is15%-20%, but it is notably greater (25%-40%) in infertile couples with male factor infertility. Varicoceles are progressive and often appear at puberty; they are more commonly found on the left side. Clinical studies have shown that fertility of some patients has not improved after varicocelectomy. Therefore, the effect of varicocelectomy is controversial. At present, traditional Chinese medicine has made some progress in the treatment of varicocele. Some traditional Chinese medicine can alleviate varicocele-induced symptoms, and improve pregnancy rates after treatment, so that some patients avoid surgery.Epimedium is a traditional Chinese medicine, and is one of the commonly drug in the treatment of reproductive endocrine disorders. Icariin is the main active ingredient of epimedium, belonging to the flavonoid compounds, which plays an important role in the regulation of the endocrine, immune, reproductive system. Experimental studies have shown that epimedium increases the weight of epididymis and seminal vesicles in prepubertal rats, and improves the levels of luteinizing hormone, and promotes testosterone secretion of rat Leydig cells in vitro. Icariin can promote the male reproductive system and reproductive endocrine function. Most of the blood supply of the testis and epididymis are the same, and both are located within the scrotum.When varicocele caused a series of pathophysiological changes in testis, epididymis can also suffer the same damage. Varicocele can cause damage of the structure and function of rat epididymis. Therefore, epididymal involvement also plays an important role in the male infertility caused by varicocele. There is no relevant paper about effects of Icariin on varicocele-induced epididymal lesions. In view of this, this experiment established an experimental varicocele model in rats. And then, icariin was used in the treatment of varicocele-induced rats. The level of oxidative stress, structure, function, and apoptosis of the epididymis were measured. We studied on effects of icariin on the epididymal lesions of varicocele-induced rats. Methods:40adolescent male SD rats were randomly divided into control group (n=10), experimental varicocele (EV) group (n=15), icariin (ICA) therapy group (n=15). Experimental varicocele model in the EV group and ICA group was established. The EV was induced by partial ligation of the left renal vein. The rats in the control group underwent a sham operation that separated the spermatic vessels without ligation. Each rat in the control group and EV group was lavaged with2ml physiological saline every day for administration6weeks. Each rat in the ICA group was lavaged with icariin (100mg/kg·d) for administration6weeks. Rats in every group were executed after6weeks. The left epididymis of every group was weighted. The level of Glutathione peroxidase (SOD), Glutathione peroxidase (GSH-Px), and Malondialdehyde (MDA) concentration were measured by Colorimetry. The contents of sialic acid were measured by spectrophotometry, and carnitine concentrations were measured by DTNB. HE stain was used to observe the microstructure changes in the epididymal tissue. Electron microscopy was used for observation of ultrastructural changes of the epididymis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method was used to detect the apoptosis of the epididymal epithelium.Results:Epididymal weight in the EV group was significantly lower than that in the control group (P<0.01). However, Epididymal weight in the ICA group was significantly higher than that in the EV group (P<0.01). Compared with the control group, the EV group showed a significant decrease in SOD and GSH-Px activity and a marked increase in the MDA concentration (P<0.01). But, the ICA group exhibited a significantly higher SOD and GSH-Px activity and lower MDA concentration than the EV group (P<0.01). Compared with the control group, microstructure and ultrastructure of the epididymis in the EV group showed pathological damage. The EV group showed irregular arrangement of cells and vacuolar-denaturalization of cytoplasm in epididymal epithelium, decrease o normal sperm in lumeno, interstitial edema, and small blood vessels congestion under the microscope. The EV group showed increased intracellular Lysosomal and volume increases, increased vacuoles in cytoplasm, mitochondria swelling and cristate clouding, basement membrane thickening under the electron microscope. Compared with the EV group, the damage of the epididymal microstructure and ultrastructure significantly alleviated. Apoptosis index (AI) of epididymal epithelium in the EV group was significantly higher than that in the control group (P<0.01). However, AI of epididymal epithelium the ICA group was significantly lower than that in the EV group (P<0.01). Sialic acid and carnitine concentrations of the epididymis in the EV group was significantly lower than that in the control group (P<0.01), respectively. However, sialic acid and carnitine concentrations of the epididymis in the ICA group was significantly higher than that in the EV group (P<0.01), respectively.Conclusions:This experiment was successful replication of experimental varicocele model in rats. Results of this study showed that varicocele could cause oxidative stress of the epididymis, and icariin inhibited its oxidative stress. Varicocele could damage the structure and function of epididymis, and icariin repaired this damage. Varicocele resulted in increases in apoptosis of epididymal epithelium, and icariin decreased the varicocele-induced apoptosis of epididymal epithelium.To sum up, our experimental preliminary confirmed that icariin could relieve varicocele-induced damage of epididymis, which provided a basis for treating infertility caused by varicocele.