The Relationship Between Sperm Androgen Receptor And Dyszoospermia Caused By Varicocele

Objective: We aimed to investigate the relationship between AR expression in sperm cells and semen quality in patients with varicocele.And to explore whether sperm AR can be used as a biomarker to screen varicocele patients with abnormal semen quality.Finally,the possible mechanism of the decrease of AR expression in patients with varicocele was explored by analyzing the relationship between p53 and AR expression in sperm cells.Methods: Body examination and ultrasound were used to identify infertile male patients with varicocele,and semen samples were collected from infertile male patients with varicocele and healthy fertile men.Semen samples were tested by sperm analysis.Western blot and quantitative real-time polymerase chain reaction(rt-PCR)were used to evaluate relative expression levels of AR and p53 in sperm cells.Pearson correlation analysis was used to reveal the correlation between AR and p53.The independent predictors of impaired spermatogenic function of varicocele were identified by multivariate Logistics analysis with results presented as Odds-Ratio(OR)and the 95% confidence intervals(95% CI).The receiver operating characteristic curve(ROC curve)was used to evaluate the value of AR as a possible biomarker in differentiating spermatic function impairment due to varicocele.Results: In the varicocele group,the average expression of AR was lower than that of the control group(p < 0.01),and the expression of p53 was higher than that of the control group(p < 0.001).The expression of AR in Grade III varicocele group was lower than that in Grade I and II(p < 0.05).The expression of AR in Grade III varicocele group was higher than that in Grade I and II(p < 0.001).In the patients with abnormal semen analysis results,the average expression of AR was 54% of that of the patients with normal semen analysis results(p < 0.01).The mean expression of p53 was 1.69 times higher than that of the normal semen group(p <0.001).Multivariate Logistic regression analysis showed that the expression level of AR in sperm was independently correlated with spermatogenic dysfunction in patients with varicocele: OR=0.14(CI 0.02-1.35,p =0.02).ROC curve showed that sperm AR had significant value in screening varicocele patients with abnormal semen quality: AUC=0.86,p < 0.001,sensitivity =81.33%,specificity =85.16%.Correlation analysis showed that AR expression was negatively correlated with p53 expression in sperm of patients with varicocele.Conclusions: The expression of AR in sperm of patients with varicocele was significantly lower than that of healthy men,and it was negatively correlated with the grade of varicocele.The decrease of AR expression may be related to impaired spermatogenic function and decreased sperm motility in patients with varicocele.The expression AR in sperm of varicocele patients with spermatogenic dysfunction was significantly lower than that of varicocele patients with normal spermatogenic function.The m RNA level of AR could be used as a potential biomarker to screen patients with varicocele with spermatogenic dysfunction.Varicocele may up-regulate p53 through hypoxiainduced HIF-1a,which eventually leads to decreasing of AR expression in testicular tissues,resulting in impaired spermatogenic function.Whether the decreasing of AR is related to the increasing of p53 in infertile varicocele patients still needs to be further verified.