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      Equine maternal aging affects the metabolomic profile of oocytes and follicular cells during different maturation time points

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          Abstract

          Introduction: Oocyte quality and fertility decline with advanced maternal age. During maturation within the ovarian follicle, the oocyte relies on the associated somatic cells, specifically cumulus and granulosa cells, to acquire essential components for developmental capacity.

          Methods: A nontargeted metabolomics approach was used to investigate the effects of mare age on different cell types within the dominant, follicular-phase follicle at three time points during maturation. Metabolomic analyses from single oocytes and associated cumulus and granulosa cells allowed correlations of metabolite abundance among cell types.

          Results and Discussion: Overall, many of the age-related changes in metabolite abundance point to Impaired mitochondrial metabolic function and oxidative stress in oocytes and follicular cells. Supporting findings include a higher abundance of glutamic acid and triglycerides and lower abundance of ceramides in oocytes and somatic follicular cells from old than young mares. Lower abundance of alanine in all follicular cell types from old mares, suggests limited anaerobic energy metabolism. The results also indicate impaired transfer of carbohydrate and free fatty acid substrates from cumulus cells to the oocytes of old mares, potentially related to disruption of transzonal projections between the cell types. The identification of age-associated alterations in the abundance of specific metabolites and their correlations among cells contribute to our understanding of follicular dysfunction with maternal aging.

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          Correlation Coefficients

          Correlation in the broadest sense is a measure of an association between variables. In correlated data, the change in the magnitude of 1 variable is associated with a change in the magnitude of another variable, either in the same (positive correlation) or in the opposite (negative correlation) direction. Most often, the term correlation is used in the context of a linear relationship between 2 continuous variables and expressed as Pearson product-moment correlation. The Pearson correlation coefficient is typically used for jointly normally distributed data (data that follow a bivariate normal distribution). For nonnormally distributed continuous data, for ordinal data, or for data with relevant outliers, a Spearman rank correlation can be used as a measure of a monotonic association. Both correlation coefficients are scaled such that they range from -1 to +1, where 0 indicates that there is no linear or monotonic association, and the relationship gets stronger and ultimately approaches a straight line (Pearson correlation) or a constantly increasing or decreasing curve (Spearman correlation) as the coefficient approaches an absolute value of 1. Hypothesis tests and confidence intervals can be used to address the statistical significance of the results and to estimate the strength of the relationship in the population from which the data were sampled. The aim of this tutorial is to guide researchers and clinicians in the appropriate use and interpretation of correlation coefficients.
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            XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification.

            Metabolite profiling in biomarker discovery, enzyme substrate assignment, drug activity/specificity determination, and basic metabolic research requires new data preprocessing approaches to correlate specific metabolites to their biological origin. Here we introduce an LC/MS-based data analysis approach, XCMS, which incorporates novel nonlinear retention time alignment, matched filtration, peak detection, and peak matching. Without using internal standards, the method dynamically identifies hundreds of endogenous metabolites for use as standards, calculating a nonlinear retention time correction profile for each sample. Following retention time correction, the relative metabolite ion intensities are directly compared to identify changes in specific endogenous metabolites, such as potential biomarkers. The software is demonstrated using data sets from a previously reported enzyme knockout study and a large-scale study of plasma samples. XCMS is freely available under an open-source license at http://metlin.scripps.edu/download/.
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              Glutamine reliance in cell metabolism

              As knowledge of cell metabolism has advanced, glutamine has been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial glutamine metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence of drug resistance, and glutaminolysis-induced metabolic reprogramming and presenting metabolic strategies to target glutamine metabolism in cancer cells. In this review, we introduce the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamine metabolism to explain why cells exhibit metabolic reliance on glutamine. Additionally, we examined whether glutamine derivatives contribute to epigenetic regulation associated with tumorigenesis. In addition, in discussing glutamine transporters, we propose a metabolic target for therapeutic intervention in cancer. Insights into how the amino acid glutamine powers cellular metabolism could pave the way for effective therapeutic strategies for ‘starving’ tumor cells. Healthy cells can manufacture enough glutamine to sustain normal function, but cancerous growth creates heavier demand for this important molecule. Jung Min Han and colleagues at Yonsei University in Incheon, South Korea have reviewed the various cellular functions of glutamine, and discuss opportunities to cut off supply and thereby derail tumor proliferation. Glutamine serves as a building block both for amino acids and nucleic acids, and is also consumed during mitochondrial energy production. Several groups are exploring the feasibility of inactivating glutamine synthesis or halting cellular uptake of this amino acid as a means of depriving cancer cells of nutrients. A deeper understanding of glutamine’s metabolic functions should accelerate progress on this front.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                25 September 2023
                2023
                : 11
                : 1239154
                Affiliations
                [1] 1 Department of Biomedical Sciences , College of Veterinary Medicine and Biomedical Sciences , Colorado State University , Fort Collins, CO, United States
                [2] 2 Department of Animal Sciences , Berry College , Mount Berry, GA, United States
                [3] 3 Proteomic and Metabolomics Core Facility , Colorado State University , Fort Collins, CO, United States
                Author notes

                Edited by: Jennifer R. Wood, University of Nebraska System, United States

                Reviewed by: Ligia Prezotto, University of Nebraska System, United States

                Luca Laghi, University of Bologna, Italy

                *Correspondence: G. D. Catandi, giovana.catandi@ 123456gmail.com ; E. M. Carnevale, elaine.carnevale@ 123456colostate.edu
                Article
                1239154
                10.3389/fcell.2023.1239154
                10561129
                37818125
                3007d9aa-81a7-48be-954b-5752e7add429
                Copyright © 2023 Catandi, Bresnahan, Peters, Fresa, Maclellan, Broeckling and Carnevale.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 June 2023
                : 28 August 2023
                Funding
                Funded by: Cecil and Irene Hylton Foundation , doi 10.13039/100016177;
                Funded by: Abney Foundation , doi 10.13039/100001437;
                This study was funded by the Cecil and Irene Hylton Foundation and the Abney Foundation Scholarship.
                Categories
                Cell and Developmental Biology
                Original Research
                Custom metadata
                Molecular and Cellular Reproduction

                mare,oocyte,age,maturation,cumulus,granulosa,follicle,metabolome
                mare, oocyte, age, maturation, cumulus, granulosa, follicle, metabolome

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