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Serum Metabolomic Profiling Identifies Characterization of Non-Obstructive Azoospermic Men.

ABSTRACT: Male infertility is considered a common health problem, and non-obstructive azoospermia with unclear pathogenesis is one of the most challenging tasks for clinicians. The objective of this study was to investigate the differential serum metabolic pattern in non-obstructive azoospermic men and to determine potential biomarkers related to spermatogenic dysfunction. Serum samples from patients with non-obstructive azoospermia (n = 22) and healthy controls (n = 31) were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Serum metabolomic profiling could differentiate non-obstructive azoospermic patients from healthy control subjects. A total of 24 metabolites were screened and identified as potential markers, many of which are involved in energy production, oxidative stress and cell apoptosis in spermatogenesis. Moreover, the results showed that various metabolic pathways, including d-glutamine and d-glutamate metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, the citrate cycle and alanine, aspartate and glutamate metabolism, were disrupted in patients with non-obstructive azoospermia. Our results indicated that the serum metabolic disorders may contribute to the etiology of non-obstructive azoospermia. This study suggested that serum metabolomics could identify unique metabolic patterns of non-obstructive azoospermia and provide novel insights into the pathogenesis underlying male infertility.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC5343775 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Serum Metabolomic Profiling Identifies Characterization of Non-Obstructive Azoospermic Men.

Zhang Zhe Z Zhang Yingwei Y Liu Changjie C Zhao Mingming M Yang Yuzhuo Y Wu Han H Zhang Hongliang H Lin Haocheng H Zheng Lemin L Jiang Hui H

International journal of molecular sciences 20170125 2

Male infertility is considered a common health problem, and non-obstructive azoospermia with unclear pathogenesis is one of the most challenging tasks for clinicians. The objective of this study was to investigate the differential serum metabolic pattern in non-obstructive azoospermic men and to determine potential biomarkers related to spermatogenic dysfunction. Serum samples from patients with non-obstructive azoospermia (<i>n</i> = 22) and healthy controls (<i>n</i> = 31) were examined using ...[more]

PMID: 28125052

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Project description:Men presenting with non-obstructive azoospermia are the most challenging clinical scenario for an infertile couple. Intracytoplasmic Sperm Injection (ICSI) with testicular sperm retrieval gave a chance for biological fatherhood once sperm can be found, but unfortunately sperm recovery rate (SSR) is something near 50%, leading to a discussion about what surgical retrieval technique is the best. Historically sperm have been retrieved using conventional Testicular Sperm Extraction (c-TESE), Testicular Sperm Aspiration (TESA), a combination of Testicular Fine Needle Aspiration (TfNA)/c-TESE, Testicular Microdissection (TM) and Open Testicular Mapping (OTEM). c-TESE published in 1995 by Devroey and cols. consists of testis delivery, a large unique albuginea incision and extraction of a portion from the majority of testicular tubules. TESA published in 1996 by Lewin and cols. is done percutaneously using a 21–23 gauge needle and a syringe to aspire testicular tubules. TfNA was published in 1965 by Obrant and Persson as an aspiration biopsy and cytological exam to verify sperm production. In 1999 Turek and cols. published the use of TfNA combined with c-TESE for sperm retrieval. In 1999, Peter Schlegel published a technique using a microsurgical approach to identify more probable sperm production areas inside the testicle that could be excised with better precision and less tissue. OTEM is a multiple biopsy approach, published in 2020 by Vieira and cols., based on TfNA principles but done at the same time without albuginea opening or surgical microscope need. Since Testicular Microdissection publication, the method became the gold standard for sperm retrieval, allowing superior SSR with minimal tissue removal, but the amount of testicular dissection to find more probable spermatogenesis areas, difficulties in comparative design studies, diversity TM results among doctors and other methods that can achieve very similar results we question TM superiority. The objective is review existing literature and discuss advantages and disadvantages of all the methods for sperm retrieval in non-obstructive azoospermia.

Project description:Background and objectivesWhile animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis.MethodsThis prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival.ResultsLevels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH.ConclusionSevere AAH is characterized by a distinct metabolic phenotype spanning multiple pathways. Metabolomics profiling revealed a panel of biomarkers for disease prognosis, and future studies are planned to validate these findings in larger cohorts of patients with severe AAH.

Project description:Novel biomarkers that more accurately reflect kidney function and predict future CKD are needed. The human metabolome is the product of multiple physiologic or pathophysiologic processes and may provide novel insight into disease etiology and progression. This study investigated whether estimated kidney function would be associated with multiple metabolites and whether selected metabolomic factors would be independent risk factors for incident CKD.In total, 1921 African Americans free of CKD with a median of 19.6 years follow-up among the Atherosclerosis Risk in Communities Study were included. A total of 204 serum metabolites quantified by untargeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry was analyzed by both linear regression for the cross-sectional associations with eGFR (specified by the Chronic Kidney Disease Epidemiology Collaboration equation) and Cox proportional hazards model for the longitudinal associations with incident CKD.Forty named and 34 unnamed metabolites were found to be associated with eGFR specified by the Chronic Kidney Disease Epidemiology Collaboration equation with creatine and 3-indoxyl sulfate showing the strongest positive (2.8 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, 2.1 to 3.5) and negative association (-14.2 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, -17.0 to -11.3), respectively. Two hundred four incident CKD events with a median follow-up time of 19.6 years were included in the survival analyses. Higher levels of 5-oxoproline (hazard ratio, 0.70; 95% confidence interval, 0.60 to 0.82) and 1,5-anhydroglucitol (hazard ratio, 0.68; 95% confidence interval, 0.58 to 0.80) were significantly related to lower risk of incident CKD, and the associations did not appreciably change when mutually adjusted.These data identify a large number of metabolites associated with kidney function as well as two metabolites that are candidate risk factors for CKD and may provide new insights into CKD biomarker identification.

Dataset Information

Serum Metabolomic Profiling Identifies Characterization of Non-Obstructive Azoospermic Men.

Publications

Serum Metabolomic Profiling Identifies Characterization of Non-Obstructive Azoospermic Men.

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