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      Metabolomic markers of fertility in bull seminal plasma

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          Abstract

          Metabolites play essential roles in biological systems, but detailed identities and significance of the seminal plasma metabolome related to bull fertility are still unknown. The objectives of this study were to determine the comprehensive metabolome of seminal plasma from Holstein bulls and to ascertain the potential of metabolites as biomarkers of bull fertility. The seminal plasma metabolome from 16 Holstein bulls with two fertility rates were determined by gas chromatography-mass spectrometry (GC-MS). Multivariate and univariate analyses of the data were performed, and the pathways associated with the seminal plasma metabolome were identified using bioinformatics approaches. Sixty-three metabolites were identified in the seminal plasma of all bulls. Fructose was the most abundant metabolite in the seminal fluid, followed for citric acid, lactic acid, urea and phosphoric acid. Androstenedione, 4-ketoglucose, D-xylofuranose, 2-oxoglutaric acid and erythronic acid represented the least predominant metabolites. Partial-Least Squares Discriminant Analysis (PLSDA) revealed a distinct separation between high and low fertility bulls. The metabolites with the greatest Variable Importance in Projection score (VIP > 2) were 2-oxoglutaric acid and fructose. Heat-map analysis, based on VIP score, and univariate analysis indicated that 2-oxoglutaric acid was less ( P = 0.02); whereas fructose was greater ( P = 0.02) in high fertility than in low fertility bulls. The current study is the first to describe the metabolome of bull seminal plasma using GC-MS and presented metabolites such as 2-oxoglutaric acid and fructose as potential biomarkers of bull fertility.

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          Innovation: Metabolomics: the apogee of the omics trilogy.

          Metabolites, the chemical entities that are transformed during metabolism, provide a functional readout of cellular biochemistry. With emerging technologies in mass spectrometry, thousands of metabolites can now be quantitatively measured from minimal amounts of biological material, which has thereby enabled systems-level analyses. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and are shaping our understanding of cell biology, physiology and medicine.
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            Metabolomics--the link between genotypes and phenotypes.

            Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the ultimate response of biological systems to genetic or environmental changes. In parallel to the terms 'transcriptome' and proteome', the set of metabolites synthesized by a biological system constitute its 'metabolome'. Yet, unlike other functional genomics approaches, the unbiased simultaneous identification and quantification of plant metabolomes has been largely neglected. Until recently, most analyses were restricted to profiling selected classes of compounds, or to fingerprinting metabolic changes without sufficient analytical resolution to determine metabolite levels and identities individually. As a prerequisite for metabolomic analysis, careful consideration of the methods employed for tissue extraction, sample preparation, data acquisition, and data mining must be taken. In this review, the differences among metabolite target analysis, metabolite profiling, and metabolic fingerprinting are clarified, and terms are defined. Current approaches are examined, and potential applications are summarized with a special emphasis on data mining and mathematical modelling of metabolism.
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                Author and article information

                Contributors
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 April 2018
                2018
                : 13
                : 4
                : e0195279
                Affiliations
                [1 ] Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS, United States of America
                [2 ] Department of Animal Sciences, Federal University of Ceara, Fortaleza, Ceara, Brazil
                [3 ] Alta Genetic Inc., Watertown, WI, United States of America
                [4 ] Department of Reproduction and Artificial Insemination, Selcuk University, Konya, Turkey
                Faculty of Animal Sciences and Food Engineering, University of São Paulo, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-8335-5645
                Article
                PONE-D-17-43230
                10.1371/journal.pone.0195279
                5892889
                29634739
                2daba148-8fc0-4e9e-bc94-7fc901d21183
                © 2018 Velho et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 December 2017
                : 19 March 2018
                Page count
                Figures: 8, Tables: 2, Pages: 20
                Funding
                Funded by: USDA National Institute of Food and Agriculture, Agriculture and Food Research Initiative Competitive Grant
                Award ID: 2017-67016-26507
                Award Recipient :
                Funded by: USDA National Institute of Food and Agriculture, Agriculture and Food Research Initiative Competitive Grant
                Award ID: 2017-67016-26507
                Award Recipient :
                Funded by: USDA NIFA Hatch
                Award ID: Accession number 1005778
                Award Recipient :
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil
                Award Recipient :
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) of Brazil
                Award Recipient :
                Funded by: Alta Genetics Inc.
                Award Recipient :
                Funded by: Mississippi Agricultural Experiment Station
                Award Recipient :
                This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2017-67016-26507 from the USDA National Institute of Food and Agriculture (NIFA). Partial funding was also provided by Mississippi Agricultural Experiment Station, Alta Genetics Inc., Hatch project under accession number 1005778 from the USDA NIFA, and by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil. A. Velho and E. Menezes were funded by competitive fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) of Brazil.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Germ Cells
                Sperm
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolites
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Carbohydrates
                Monosaccharides
                Fructoses
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Carbohydrates
                Monosaccharides
                Fructoses
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Carbohydrate Metabolism
                Research and Analysis Methods
                Chromatographic Techniques
                Gas Chromatography-Mass Spectrometry
                Physical Sciences
                Chemistry
                Analytical Chemistry
                Mass Spectrometry
                Gas Chromatography-Mass Spectrometry
                Research and Analysis Methods
                Spectrum Analysis Techniques
                Mass Spectrometry
                Gas Chromatography-Mass Spectrometry
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolomics
                Computer and Information Sciences
                Network Analysis
                Metabolic Networks
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Phosphoric Acids
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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