Cumulus cell acetyl-CoA metabolism from acetate is associated with maternal age but inconclusively with oocyte maturity
Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but...
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Published in | Systems biology in reproductive medicine Vol. 68; no. 1; pp. 36 - 43 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
28.12.2021
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Online Access | Get full text |
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Abstract | Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but data on the use of other potential carbon substrates are lacking in humans. This prospective and blinded cohort study was designed to examine the substrate utilization of CCs by age and oocyte competence. Individual sets of CC clumps from participants were removed after oocyte retrieval procedure, incubated with stable isotope labeled substrates, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA. The acyl-chain of acetyl-CoA contains 2 carbons that can be derived from
13
C-labeled substrates resulting in an M+2 isotopologue that contains 2
13
C atoms. Comparing the fate of three major carbon sources, mean enrichment of M+2 acetyl-CoA (mean, standard deviation) was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Due to this unexpected high and variable labeling from acetate, we then examined acetyl-CoA mean % enrichment from acetate of in 278 CCs from 21 women ≤34 (49.06, 12.73) decreased with age compared to 124 CCs from 10 women >34 (43.48, 16.20) (p=0.0004, t-test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M+2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: −6.02, CI: −1.74,−13.79, p=0.013). Acetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of non-glucose substrates should be investigated relative to oocyte function and age-related fertility. |
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AbstractList | Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but data on the use of other potential carbon substrates are lacking in humans. This prospective and blinded cohort study was designed to examine the substrate utilization of CCs by age and oocyte competence. Individual sets of CC clumps from participants were removed after oocyte retrieval procedure, incubated with stable isotope labeled substrates, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA. The acyl-chain of acetyl-CoA contains 2 carbons that can be derived from
13
C-labeled substrates resulting in an M+2 isotopologue that contains 2
13
C atoms. Comparing the fate of three major carbon sources, mean enrichment of M+2 acetyl-CoA (mean, standard deviation) was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Due to this unexpected high and variable labeling from acetate, we then examined acetyl-CoA mean % enrichment from acetate of in 278 CCs from 21 women ≤34 (49.06, 12.73) decreased with age compared to 124 CCs from 10 women >34 (43.48, 16.20) (p=0.0004, t-test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M+2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: −6.02, CI: −1.74,−13.79, p=0.013). Acetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of non-glucose substrates should be investigated relative to oocyte function and age-related fertility. |
Author | Orris, John J. Doan, Mary T. Anderson, Sharon Frey, Alexander J. Clements, Nicolle Goodspeed, Jason R. Xu, Peining Snyder, Nathaniel W. Glassner, Michael J. |
AuthorAffiliation | 4- Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA 3- AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 2- Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA 5- Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA 1- Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 |
AuthorAffiliation_xml | – name: 2- Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA – name: 3- AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 – name: 5- Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – name: 1- Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 – name: 4- Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA |
Author_xml | – sequence: 1 givenname: Sharon surname: Anderson fullname: Anderson, Sharon organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – sequence: 2 givenname: Peining surname: Xu fullname: Xu, Peining organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – sequence: 3 givenname: Alexander J. surname: Frey fullname: Frey, Alexander J. organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – sequence: 4 givenname: Jason R. surname: Goodspeed fullname: Goodspeed, Jason R. organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – sequence: 5 givenname: Mary T. surname: Doan fullname: Doan, Mary T. organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – sequence: 6 givenname: John J. surname: Orris fullname: Orris, John J. organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – sequence: 7 givenname: Nicolle surname: Clements fullname: Clements, Nicolle organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – sequence: 8 givenname: Michael J. surname: Glassner fullname: Glassner, Michael J. organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA – sequence: 9 givenname: Nathaniel W. surname: Snyder fullname: Snyder, Nathaniel W. organization: Main Line Fertility, 825 Old Lancaster Road, Suite 170, Bryn Mawr, PA 19010 Ob/Gyn Department, Drexel University College of Medicine, Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA, USA AJ Drexel Autism Institute, Drexel University, 3020 Market St Suite 560, Philadelphia, PA 19104 Center for Metabolic Disease Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine. Philadelphia, PA, USA Department of Decision System Sciences, St. Joes University, 348 Mandeville Hall, Philadelphia, PA, USA |
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Notes | Authors’ Contribution Conducted experiments and analyzed data: PX, AJF, JRG, MTD; analyzed data: NC; conducted experiments and obtained samples: SA, JJO, MJG; wrote the manuscript, obtained funding, conducted experiments, and analyzed data: SA and NWS. |
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Title | Cumulus cell acetyl-CoA metabolism from acetate is associated with maternal age but inconclusively with oocyte maturity |
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