Study Of Epididymis Hypoxia And Dysfunction Of Varicocele Rat

AimThrough building the varicocele animal model, to investigated the expression of hypoxia induced factor 1 alpha (HIF-1α) and p53 of epididymis epithelium and contents of sialic acid and carnitine in the epididymis of experimental model of varicocele, to study the pathophysiological changes that induced by varicocele and shed some light on the mechanism of how varicocele induces infertility.MethodsA total of 30 wister rats were randomly divided into three groups, namely control group (10 rats, controls), experimental group (10 rats, partly ligation of the left renal vein) and sham group (10 rats, do same to the rats of experimental group except ligation of the left renal vein). 3 rats of the experimental group, 1 rat of the sham group and 3 rats of the control group were excluded because of death, failure of the model and original varicocele. All of the rest rats were sacrificed to get epididymises 49 days after the surgery. HIF-laexpression was detected with immunohistochemical technique and western blot, the contents of sialic acid by spectrophotometry, the carnitine content with DTNB, the P53 with immunohistochemical technique in each epididymis.ResultsThe positive p53 expression rate of epididymis epithelium in experimental group was significantly higher than that of control group(P<0.05); HIF-1αexpression in the epididymis of experimental group, detected with western blot, was significantly higher than that of sham and control groups (P < 0.05). HIF-1αwas expressed in almost every epdidymis epithelium cell detected with immunohistochemical technique. And the association between the contents of carnitine and sialic acid and relative HIF-αexpression in the epididymises of experimental group rats are significantly negative(r=-0. 791, p=0. 034; r=-0. 846, p=0. 017).Conclusion1. Varicocele can significantly reduce the contents of epididymis' carnitine and sialic acid, which represent the epididymis function. And epididymis is the place where sperm became mature. So varicocele can interrupt the process of the sperm maturity through destroying the epididymis function.2. The the significantly high HIF-αexpression in varicocele rats, epididymis show that varicocele can cause epididymis dysfunction as well as hypoxia.3. As the HIF-1αexpression stands for the the degree of hypoxia, the negative relation between the level of HIF-1αexpression and epididymal function, tells us that epididymis hypoxia plays an important role in the process of epididymis dysfunction, which is one of the reason to cause infertility. But HIF-1αcan also do something good for tissue to cure the damage of hypoxia through up-regulating many proteins. So the negative relation between the level of HIF-1αexpression and epididymal function also indicates that HIF-1αplays the role of damaging the function of epididymis in the pathophysiological process of varicocele. Considering the previous studies, the damage caused by HIF-1αis probably through inducing cell apoptosis.4. Increased p53 expression in epididymal epithelium cell caused by varicocele indicates that p53 may play an important role in the process of epididymis dysfunction caused by epididymis hypoxia. And probably involved in the process of HIF-1αinduced apoptosis. SignificantThis study creates a new way to explain the pathophysiology of varicocele from the epididymis aspect. And shed some light on the process of varicocele induced infertility. This can give some supports on the improvement of varicocele treatments.