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Effects of varicocele and microsurgical varicocelectomy on the metabolites in semen.

ABSTRACT: The influence of varicocele and microsurgical varicocelectomy on semen quality remains unclear. Few studies have investigated the relationship between semen metabolism and the abnormalities in reproductive function caused by varicocele, however, there is no study on the changes of semen metabolism after microsurgical varicocelectomy. Here, we used the non-targeted and targeted metabolic analysis to investigate the different metabolites in seminal plasma within normal, varicocele, and varicocelectomy groups. We clearly showed that varicocele significantly affects semen metabolism, and microsurgical varicocelectomy can reverse this metabolic abnormality. Moreover, we characterized the landscape of three dipeptides in the seminal plasma of patients with varicocele that have not been identified previously in human tissues or biofluids. Interestingly, the levels of these three dipeptides decreased after microsurgical varicocelectomy coincident with an improvement in semen quality. Western blotting confirmed the downregulation of DPEP3 (dipeptidase 3) in the varicocele group and the upregulation of DPEP3 in the varicocelectomy group. Furthermore, we found that eight metabolites may be helpful to distinguish varicocele patients from normal subjects. Our results may be applied to earlier diagnosis or to predict the outcome of microsurgery for varicocele.

SUBMITTER: Zhang X

PROVIDER: S-EPMC8956711 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Effects of varicocele and microsurgical varicocelectomy on the metabolites in semen.

Zhang Xinzong X Deng Cuncan C Liu Wujiang W Liu Huang H Zhou Yu Y Li Qianyi Q Zheng Houbin H Wang Qiling Q Jiang Min M Pang Tao T Ma Chunjie C Huang Cheng C Zhao Qingguo Q Tang Yunge Y

Scientific reports 20220325 1

The influence of varicocele and microsurgical varicocelectomy on semen quality remains unclear. Few studies have investigated the relationship between semen metabolism and the abnormalities in reproductive function caused by varicocele, however, there is no study on the changes of semen metabolism after microsurgical varicocelectomy. Here, we used the non-targeted and targeted metabolic analysis to investigate the different metabolites in seminal plasma within normal, varicocele, and varicocelec ...[more]

PMID: 35338186

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Project description:BackgroundVaricocele (VC) is one of the most common causes of infertility in men, and microscopic varicocelectomy is currently the major surgical procedure for VC. We assessed the clinical effectiveness of microsurgical subinguinal varicocelectomy (MSV) with enhanced recovery after surgery (ERAS) in the treatment of VC in terms of semen quality improvement rate, pregnancy rate, pain relief rate, recurrence rate, and complication rate after MSV and explored the indications for VC surgery.MethodsIn total, 216 patients undergoing MSV in our center between June 2019 and July 2020 were enrolled in this study. All patients received the surgery under local anesthesia and were admitted and discharged within 24 hours. All patients were followed up for more than 6 months, and the rates of semen quality improvement, pregnancy, pain relief, recurrence, and postoperative complications were recorded. We can evaluate the pain degree of patients through the numerical rating scale (NRS). (I) 0 points for painless; (II) 1-3: mild pain; (III) 4-6: moderate pain; (IV) 7-10 points are severe pain. 0 is the most slightly, indicating comfort, and 10 is the most painful and unbearable.ResultsThe sperm concentration, total sperm count, progressive motility rate, sperm viability, and morphology were significantly improved after the surgery (all P values <0.05). The rate of semen quality improvement was 88.2%, and the semen indicators returned to normal in 26.6% of the patients. Among the patients who were followed up for 1 year, the natural conception rate reached 27.1% and was accompanied by a 95.5% pain relief rate, a 0.5% VC recurrence rate, and a 2.3% postoperative complication rate.We obtained data through laboratory examination of semen DNA fragments index (DFI). Compared with preoperative and postoperative DFI, postoperative DFI was improved, and the pregnancy outcome was improved.ConclusionsMSV under local anesthesia increases the rates of semen quality improvement, pregnancy, and pain relief while lowering the rates of recurrence and postoperative complications. MSV may also help to improve the pregnancy outcomes in patients with VC accompanied by sperm DNA fragmentation or nonobstructive azoospermia, but this should be verified by further investigation.

Project description:BackgroundVaricocele is a significant but treatable contributor to male infertility. The efficacy of varicocelectomy in improving sperm quality is not consistent, with only 60-80% of patients experiencing improved semen quality. This prospective cohort study aimed to evaluate the effect of microscopic subinguinal varicocelectomy (MSV) on testicular arterial blood flow volume (TABFV) and to determine the value of preoperative TABFV in predicting the outcome of MSV.MethodsPatients with varicocele who underwent MSV at the same clinical center between July 2020 and April 2023 were enrolled. All patients underwent ultrasound assessment and at least one semen analysis before and after MSV. Both univariate and multivariate logistic regression analyses were performed to assess the association between pre-MSV variables and semen improvement after MSV. Subsequently, a diagnostic model was developed.ResultsThis study enrolled 96 patients with varicocele, including 31 who showed semen improvement after MSV and 65 who did not. The postoperative semen-improved group demonstrated a significant increase in TABFV of the right testis (TABFV-R) and left testis (TABFV-L) (P<0.001). Notably, the postoperative TABFV-L was more than twice the preoperative TABFV-L. Preoperative TABFV-R and a combination of subclinical right-sided varicocele were found to be associated with semen improvement after MSV, and a diagnostic model was developed using these two variables. The diagnostic model exhibited satisfactory performance, with an area under the curve (AUC) of 0.824 [95% confidence interval (CI): 0.735-0.913], which was further validated internally yielding an AUC of 0.824 (95% CI: 0.726-0.900). Additionally, calibration analysis confirmed that the diagnostic model was well calibrated, and the Hosmer-Lemeshow test resulted in a P value of 0.794. The decision curve demonstrated that using this proposed nomogram would yield a net benefit if the threshold probability for semen improvement after MSV exceeded 10%.ConclusionsTABFV-L demonstrated potential utility in clinical practice for assessing outcomes of MSV, and the diagnostic model incorporating TABFV-R and a combination of right-side varicocele performed well in predicting improvements in semen parameters following MSV.

Project description:PurposeTo verify if the presence of varicocele (grades II and III) with and without seminal alterations, using the 5th centile cutoff values in table A1.1 of the World Health Organization (WHO, 2010) manual, alters the seminal plasma levels of proteins DNASE1 (deoxyribonuclease-1) and IGFBP7 (Insulin-like growth factor-binding protein 7), which are related to apoptosis regulation and cell proliferation, respectively, demonstrating that these proteins are important for correct spermatogenesis.MethodsThis cross sectional study was performed at the Sao Paulo Federal University Paulo between May 2014 and April 2016. A total of 61 male adolescents were included in this study, of which 20 controls without varicocele (C), 22 with varicocele and normal semen analysis (VNS) and 19 with varicocele and altered semen analysis (VAS). Seminal plasma from each patient was used for Western blotting analysis of individual protein levels. Values of each protein were normalized to a testicular housekeeping protein (PARK7-protein deglycase DJ-1).ResultsLevels of IGFBP7 protein are increased in varicocele. Levels of DNASE1 are progressively decreased in varicocele (lower in varicocele and normal semen analysis, lowest in varicocele and altered semen analysis) when compared to adolescents without varicocele. DNASE1 levels are positively correlated with sperm concentration and morphology (correlation values of 0.400 and 0.404, respectively; p values of 0.001 and 0.001, respectively).ConclusionIn conclusion, in adolescents, seminal plasma levels of IGFBP7, responsible for proliferative activity, are increased in varicocele grades II and III, and DNASE1, responsible for apoptosis regulation, are lower in varicocele, lowest in varicocele and low semen quality. These proteins demonstrate molecular alterations brought upon by varicocele. Moreover, DNASE1 is capable of discriminating a varicocele that causes alterations to semen quality from one that does not. We propose that the initial response of varicocele is to increase proliferative activity which, if followed by regulation of apoptosis, may lead to the ejaculation of a population of sperm that are in accordance with WHO cutoff values but, in the presence of dysregulated apoptosis, leads to lower sperm concentration and morphology.

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Effects of varicocele and microsurgical varicocelectomy on the metabolites in semen.

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Effects of varicocele and microsurgical varicocelectomy on the metabolites in semen.

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