Seminal plasma untargeted metabolomic and lipidomic profiling for the identification of a novel panel of biomarkers and therapeutic targets related to male infertility
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ABSTRACT:
SUBMITTER: Correnti S
PROVIDER: S-EPMC10565040 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Although piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis, little is known about piRNAs in the seminal plasma of infertile males. In this study, we systematically investigated the profiles of seminal plasma piRNAs in infertile males to identify piRNAs that are altered during infertility and evaluate their diagnostic value. Seminal plasma samples were obtained from 211 infertile patients (asthenozoospermia and azoospermia) and 91 fertile controls. High-throughput sequencing technology was employed to screen piRNA profiles in seminal plasma samples pooled from healthy controls and infertile patients. The results identified 61 markedly altered piRNAs in infertile patient groups compared with control group. Next, a quantitative RT-PCR assay was conducted in the training and validation sets to measure and confirm the concentrations of altered piRNAs. The results identified a panel of 5 piRNAs that were significantly decreased in seminal plasma of infertile patients compared with healthy controls. ROC curve analysis and risk score analysis revealed that the diagnostic potential of these 5 piRNAs to distinguish asthenozoospermic and azoospermic individuals from healthy controls was high. In summary, this study identifies a panel of piRNAs that can accurately distinguish fertile from infertile males. This finding may provide pathophysiological clues about the development of infertility.
| S-EPMC4828650 | biostudies-literature
Project description:Although piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis, little is known about piRNAs in the seminal plasma of infertile males. In this study, we systematically investigated the profiles of seminal plasma piRNAs in infertile males to identify piRNAs that are altered during infertility and evaluate their diagnostic value. Seminal plasma samples were obtained from 211 infertile patients (asthenozoospermia and azoospermia) and 91 fertile controls. High-throughput sequencing technology was employed to screen piRNA profiles in seminal plasma samples pooled from healthy controls and infertile patients. The results identified 61 markedly altered piRNAs in the infertile patient groups compared with the control group. Next, a quantitative RT-PCR assay was conducted in the training and validation sets to measure and confirm the concentrations of altered piRNAs. The results identified a panel of 5 piRNAs that were significantly decreased in the seminal plasma of infertile patients compared with healthy controls. The areas under the ROC curves for these piRNAs ranged from 0.796 to 0.996, suggesting that the diagnostic potential of these 5 piRNAs to distinguish asthenozoospermic and azoospermic individuals from healthy controls was high. In summary, this study identifies a panel of piRNAs that can accurately distinguish fertile from infertile males. This finding may provide pathophysiological clues that are involved in the development of infertility. Fresh samples were collected and stored at -80â??.Total RNA of seminal plasma were extracted and solexa sequencing was performed.
2016-06-28 | E-GEOD-78131 | biostudies-arrayexpress
Project description:Although piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis, little is known about piRNAs in the seminal plasma of infertile males. In this study, we systematically investigated the profiles of seminal plasma piRNAs in infertile males to identify piRNAs that are altered during infertility and evaluate their diagnostic value. Seminal plasma samples were obtained from 211 infertile patients (asthenozoospermia and azoospermia) and 91 fertile controls. High-throughput sequencing technology was employed to screen piRNA profiles in seminal plasma samples pooled from healthy controls and infertile patients. The results identified 61 markedly altered piRNAs in the infertile patient groups compared with the control group. Next, a quantitative RT-PCR assay was conducted in the training and validation sets to measure and confirm the concentrations of altered piRNAs. The results identified a panel of 5 piRNAs that were significantly decreased in the seminal plasma of infertile patients compared with healthy controls. The areas under the ROC curves for these piRNAs ranged from 0.796 to 0.996, suggesting that the diagnostic potential of these 5 piRNAs to distinguish asthenozoospermic and azoospermic individuals from healthy controls was high. In summary, this study identifies a panel of piRNAs that can accurately distinguish fertile from infertile males. This finding may provide pathophysiological clues that are involved in the development of infertility.
2016-06-28 | GSE78131 | GEO
Project description:Seminal extracellular vesicles (SemEVs) are repositories of biomolecules, including metabolites involved in the regulation of sperm function. The correlation between the metabolite profile of SemEVs and semen parameters, along with their role in regulating sperm function, is an unexplored area. This preliminary study evaluated the metabolomic content of SemEVs. Semen samples were obtained from 18 healthy men, and SemEVs were extracted from seminal plasma using the size exclusion chromatography qEV Gen 2-35 nm column coupled with an automatic fraction collector. The physical characterization of SemEVs was carried out with the ZetaView PMX-430-Z QUATT laser system. EV protein markers were detected using Western blot. In addition, these SemEVs were used for metabolomic profiling and functional bioinformatic analysis. The mean concentration of isolated SemEVs was 1.7 ± 1.1 × 1011/mL of seminal plasma, whereas SemEVs size and zeta potential were 129.5 ± 5.5 nm and -40.03 ± 3.99 mV, respectively. Western blot analysis confirmed the presence of EV specific markers such as CD81, ALIX, and TSG101. A total of 107 metabolites were identified using this untargeted metabolomic approach in SemEVs. Bioinformatics analysis further revealed that metabolites associated with tyrosine metabolism were highly enriched in these SemEVs. Ingenuity Pathway Analysis (IPA) also indicated that these metabolites present in SemEVs were involved in the regulation of the free radical scavenging pathway. Furthermore, our metabolomic results suggest that these SemEV-associated metabolites may play a pivotal role in the maintenance of seminal plasma redox homeostasis.
| S-EPMC11506783 | biostudies-literature
Project description:we reported the seminal plasma piRNA change of infertility patients
2021-02-27 | GSE167592 | GEO
Project description:AimThis study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility.MethodsFrom September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022.ResultsOur analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR < 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744.ConclusionThe PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men.
| S-EPMC10240070 | biostudies-literature
Project description:We used a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach to obtain the metabolic profiling of unexplained male infertility (UMI), and identified seminal plasma biomarkers associated with UMI by a two-stage population study. A robust OPLS-DA model based on these identified metabolites was able to distinguish 82% of the UMI patients from health controls with a specificity of 92%. In this model, 44 metabolites were found differentially expressed in UMI subjects compared with health controls. By pathway enrichment analysis, we identified several major changed metabolic pathways related to UMI. Our findings provide new perspective for the diagnosis of UMI.
| S-EPMC5552325 | biostudies-other
Project description:BackgroundMetabolomic approaches, which include the study of low molecular weight molecules, are an emerging -omics technology useful for identification of biomarkers. In this field, nuclear magnetic resonance (NMR) spectroscopy has already been used to uncover (in) fertility biomarkers in the seminal plasma (SP) of several mammalian species. However, NMR studies profiling the porcine SP metabolome to uncover in vivo fertility biomarkers are yet to be carried out. Thus, this study aimed to evaluate the putative relationship between SP-metabolites and in vivo fertility outcomes. To this end, 24 entire ejaculates (three ejaculates per boar) were collected from artificial insemination (AI)-boars throughout a year (one ejaculate every 4 months). Immediately after collection, ejaculates were centrifuged to obtain SP-samples, which were stored for subsequent metabolomic analysis by NMR spectroscopy. Fertility outcomes from 1525 inseminations were recorded over a year, including farrowing rate, litter size, stillbirths per litter and the duration of pregnancy.ResultsA total of 24 metabolites were identified and quantified in all SP-samples. Receiver operating characteristic (ROC) curve analysis showed that lactate levels in SP had discriminative capacity for farrowing rate (area under the curve [AUC] = 0.764) while carnitine (AUC = 0.847), hypotaurine (AUC = 0.819), sn-glycero-3-phosphocholine (AUC = 0.833), glutamate (AUC = 0.799) and glucose (AUC = 0.750) showed it for litter size. Similarly, citrate (AUC = 0.743), creatine (AUC = 0.812), phenylalanine (AUC = 0.750), tyrosine (AUC = 0.753) and malonate (AUC = 0.868) levels had discriminative capacity for stillbirths per litter; and malonate (AUC = 0.767) and fumarate (AUC = 0.868) levels for gestation length.ConclusionsThe assessment of selected SP-metabolites in ejaculates through NMR spectroscopy could be considered as a promising non-invasive tool to predict in vivo fertility outcomes in pigs. Moreover, supplementing AI-doses with specific metabolites should also be envisaged as a way to improve their fertility potential.
| S-EPMC8588628 | biostudies-literature
Project description:Male infertility is a rising problem and the etiology at the molecular level is unclear. Use of omics has provided an insight into the underlying cellular changes in the spermatozoa of infertile men. Proteomics is one the promising omics techniques for biomarker screening that can provide complete information on molecular processes associated with male infertility. Varicocele is a pressing issue in the field of male infertility and the search for an appropriate diagnostic and therapeutic biomarker is still ongoing. In this review, we discuss the reports on proteomic profiles of sperm and seminal plasma in male infertility and provide an in-depth insight into varicocele studies associated with male infertility.
| S-EPMC7502311 | biostudies-literature
Project description:Acute leukemias (AL) are aggressive neoplasms with high mortality rates. Metabolomics and oxidative status have emerged as important tools to identify new biomarkers with clinical utility. To identify the metabolic differences between healthy individuals (HI) and patients with AL, a multiplatform untargeted metabolomic and lipidomic approach was conducted using liquid and gas chromatography coupled with quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS or GC-QTOF-MS). Additionally, the total antioxidant capacity (TAC) was measured. A total of 20 peripheral blood plasma samples were obtained from patients with AL and 18 samples from HI. Our analysis revealed 135 differentially altered metabolites in the patients belonging to 12 chemical classes; likewise, the metabolic pathways of glycerolipids and sphingolipids were the most affected in the patients. A decrease in the TAC of the patients with respect to the HI was evident. This study conducted with a cohort of Colombian patients is consistent with observations from other research studies that suggest dysregulation of lipid compounds. Furthermore, metabolic differences between patients and HI appear to be independent of lifestyle, race, or geographic location, providing valuable information for future advancements in understanding the disease and developing more global therapies.
| S-EPMC10667492 | biostudies-literature