{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:15:22Z","timestamp":1777504522606,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center","award":["2017\/27\/B\/NZ9\/00904"],"award-info":[{"award-number":["2017\/27\/B\/NZ9\/00904"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Glucose or fatty acids (FAs) metabolisms may alter the ovarian follicle environment and thus determine oocyte and the nascent embryo quality. The aim of the experiment was to investigate the effect of selective inhibition of glucose (iodoacetate + DHEA) or FA (etomoxir) metabolism on in vitro maturation (IVM) of bovine COCs (cumulus\u2013oocyte complexes) to investigate oocyte\u2019s development, quality, and energy metabolism. After in vitro fertilization, embryos were cultured to the blastocyst stage. Lipid droplets, metabolome, and lipidome were analyzed in oocytes and cumulus cells. mRNA expression of the selected genes was measured in the cumulus cells. ATP and glutathione relative levels were measured in oocytes. Changes in FA content in the maturation medium were evaluated by mass spectrometry. Our results indicate that only glucose metabolism is substantial to the oocyte during IVM since only glucose inhibition decreased embryo culture efficiency. The most noteworthy differences in the reaction to the applied inhibition systems were observed in cumulus cells. The upregulation of ketone body metabolism in the cumulus cells of the glucose inhibition group suggest possibly failed attempts of cells to switch into lipid consumption. On the contrary, etomoxir treatment of the oocytes did not affect embryo development, probably due to undisturbed metabolism in cumulus cells. Therefore, we suggest that the energy pathways analyzed in this experiment are not interchangeable alternatives in bovine COCs.<\/jats:p>","DOI":"10.3390\/genes12060838","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:22:15Z","timestamp":1622420535000},"page":"838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Response of Bovine Cumulus\u2013Oocytes Complexes to Energy Pathway Inhibition during In Vitro Maturation"],"prefix":"10.3390","volume":"12","author":[{"given":"Paulina","family":"Lipinska","sequence":"first","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-624 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7642-0787","authenticated-orcid":false,"given":"Ewa","family":"Sell-Kubiak","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-624 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3489-1684","authenticated-orcid":false,"given":"Piotr","family":"Pawlak","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-624 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9649-2422","authenticated-orcid":false,"given":"Zofia Eliza","family":"Madeja","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-624 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-791X","authenticated-orcid":false,"given":"Ewelina","family":"Warzych","sequence":"additional","affiliation":[{"name":"Department of Genetics and Animal Breeding, Poznan University of Life Sciences, 60-624 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00018-014-1739-4","article-title":"Metabolic Control of Oocyte Development: Linking Maternal Nutrition and Reproductive Outcomes","volume":"72","author":"Gu","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.14202\/vetworld.2016.91-100","article-title":"Potential of Acute Phase Proteins as Predictor of Postpartum Uterine Infections During Transition Period and Its Regulatory Mechanism in Dairy Cattle","volume":"9","author":"Manimaran","year":"2016","journal-title":"Vet. World"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1071\/RD14363","article-title":"Nutrition and Maternal Metabolic Health in Relation to Oocyte and Embryo Quality: Critical Views on What We Learned from the Dairy Cow Model","volume":"27","author":"Leroy","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1095\/biolreprod.112.106062","article-title":"Bovine Cumulus Cells Protect Maturing Oocytes from Increased Fatty Acid Levels by Massive Intracellular Lipid Storage","volume":"88","author":"Aardema","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1095\/biolreprod.114.120634","article-title":"The Cumulus Cell Layer Protects the Bovine Maturing Oocyte against Fatty Acid-Induced Lipotoxicity","volume":"92","author":"Lolicato","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.3168\/jds.2013-7278","article-title":"Genetic Merit for Fertility Traits in Holstein Cows: Iv. Transition Period, Uterine Health, and Resumption of Cyclicity","volume":"97","author":"Moore","year":"2014","journal-title":"J. Dairy Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1016\/j.theriogenology.2011.12.008","article-title":"Utilization of Endogenous Fatty Acid Stores for Energy Production in Bovine Preimplantation Embryos","volume":"77","author":"Feil","year":"2012","journal-title":"Theriogenology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/humupd\/dmaa043","article-title":"Metabolic Co-Dependence of the Oocyte and Cumulus Cells: Essential Role in Determining Oocyte Developmental Competence","volume":"27","author":"Richani","year":"2020","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1530\/jrf.0.1160373","article-title":"Triglyceride Content of Bovine Oocytes and Early Embryos","volume":"116","author":"Ferguson","year":"1999","journal-title":"J. Reprod. Fertil."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yuan, B., Liang, S., Kwon, J.W., Jin, Y.X., Park, S.H., Wang, H.Y., Sun, T.Y., Zhang, J.B., and Kim, N.H. (2016). The Role of Glucose Metabolism on Porcine Oocyte Cytoplasmic Maturation and Its Possible Mechanisms. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168329"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20764","DOI":"10.1038\/srep20764","article-title":"Effects of Glucose Metabolism During in Vitro Maturation on Cytoplasmic Maturation of Mouse Oocytes","volume":"6","author":"Xie","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bertevello, P.S., Teixeira-Gomes, A.P., Seyer, A., Vitorino Carvalho, A., Labas, V., Blache, M.C., Banliat, C., Cordeiro, L., Duranthon, V., and Papillier, P. (2018). Lipid Identification and Transcriptional Analysis of Controlling Enzymes in Bovine Ovarian Follicle. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103261"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.theriogenology.2016.08.007","article-title":"Prepubertal Heifers Versus Cows-the Differences in the Follicular Environment","volume":"87","author":"Warzych","year":"2017","journal-title":"Theriogenology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1095\/biolreprod.110.088815","article-title":"Oleic Acid Prevents Detrimental Effects of Saturated Fatty Acids on Bovine Oocyte Developmental Competence","volume":"85","author":"Aardema","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15306","DOI":"10.1038\/s41598-018-33550-4","article-title":"The Consequences of Porcine Ivm Medium Supplementation with Follicular Fluid Become Reflected in Embryo Quality, Yield and Gene Expression Patterns","volume":"8","author":"Pawlak","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1210\/me.2014-1049","article-title":"Fatty Acid Synthesis and Oxidation in Cumulus Cells Support Oocyte Maturation in Bovine","volume":"28","author":"Brisard","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1262\/jrd.2019-102","article-title":"Energy Metabolism of Follicular Environment During Oocyte Growth and Maturation","volume":"66","author":"Warzych","year":"2020","journal-title":"J. Reprod. Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.theriogenology.2015.02.016","article-title":"Transcript Abundance, Glutathione and Apoptosis Levels Differ between Porcine Oocytes Collected from Prepubertal and Cyclic Gilts","volume":"84","author":"Pawlak","year":"2015","journal-title":"Theriogenology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/biolre\/ioaa045","article-title":"Fatty Acid Induced Lipolysis Influences Embryo Development, Gene Expression and Lipid Droplet Formation in the Porcine Cumulus Cells","volume":"103","author":"Pawlak","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1194\/jlr.D700041-JLR200","article-title":"Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics","volume":"49","author":"Matyash","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14.12.1","DOI":"10.1002\/0471250953.bi1412s43","article-title":"LipidXplorer: Software for Quantitative Shotgun Lipidomics Compatible with Multiple Mass Spectrometry Platforms","volume":"43","author":"Herzog","year":"2013","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/01621459.1952.10483441","article-title":"Use of Ranks in One-Criterion Variance Analysis","volume":"47","author":"Kruskal","year":"1952","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/00401706.1964.10490181","article-title":"Multiple Comparisons Using Rank Sums","volume":"6","author":"Dunn","year":"1964","journal-title":"Technometrics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.anireprosci.2014.07.015","article-title":"Reduced Oocyte and Embryo Quality in Response to Elevated Non-Esterified Fatty Acid Concentrations: A Possible Pathway to Subfertility?","volume":"149","author":"Bols","year":"2014","journal-title":"Anim. Reprod. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1095\/biolreprod.113.108548","article-title":"Comparative Importance of Fatty Acid \u03b2-Oxidation to Nuclear Maturation, Gene Expression, and Glucose Metabolism in Mouse, Bovine, and Porcine Cumulus Oocyte Complexes","volume":"88","author":"Paczkowski","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1530\/REP-09-0345","article-title":"The Pivotal Role of Glucose Metabolism in Determining Oocyte Developmental Competence","volume":"139","author":"Gilchrist","year":"2010","journal-title":"Reproduction"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Reader, K.L., Stanton, J.L., and Juengel, J.L. (2017). The Role of Oocyte Organelles in Determining Developmental Competence. Biology, 6.","DOI":"10.3390\/biology6030035"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1095\/biolreprod.110.084145","article-title":"\u03b2-Oxidation Is Essential for Mouse Oocyte Developmental Competence and Early Embryo Development","volume":"83","author":"Dunning","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1530\/REP-14-0015","article-title":"Fatty Acid Metabolism During Maturation Affects Glucose Uptake and Is Essential to Oocyte Competence","volume":"148","author":"Paczkowski","year":"2014","journal-title":"Reproduction"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.1210\/en.2012-2140","article-title":"Dhea-Mediated Inhibition of the Pentose Phosphate Pathway Alters Oocyte Lipid Metabolism in Mice","volume":"154","author":"Jimenez","year":"2013","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E599","DOI":"10.1152\/ajpendo.00469.2012","article-title":"Absence of Cumulus Cells During in Vitro Maturation Affects Lipid Metabolism in Bovine Oocytes","volume":"304","author":"Auclair","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1530\/rep.0.1220131","article-title":"Lipid and Fatty Acid Analysis of Fresh and Frozen-Thawed Immature and in Vitro Matured Bovine Oocytes","volume":"122","author":"Kim","year":"2001","journal-title":"Reproduction"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ydbio.2004.11.027","article-title":"Oocyte Control of Metabolic Cooperativity between Oocytes and Companion Granulosa Cells: Energy Metabolism","volume":"279","author":"Sugiura","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_34","unstructured":"Rodwell, V.W., Bender, D., Botham, K.M., Weil, P.A., and Kennelly, P.J. (2018). Harpers Ilustrated Biochemistry, McGraw-Hill Medical. [31st ed.]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S232","DOI":"10.1016\/j.theriogenology.2007.04.006","article-title":"Influence of Negative Energy Balance on Cyclicity and Fertility in the High Producing Dairy Cow","volume":"68","author":"Wathes","year":"2007","journal-title":"Theriogenology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13766","DOI":"10.1038\/s41598-018-31822-7","article-title":"Metabolic Gene Expression and Epigenetic Effects of the Ketone Body \u0392-Hydroxybutyrate on H3k9ac in Bovine Cells, Oocytes and Embryos","volume":"8","author":"Sangalli","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.20463\/jenb.2016.06.20.2.5","article-title":"Characterization of the Metabolic Effect of \u0392-Alanine on Markers of Oxidative Metabolism and Mitochondrial Biogenesis in Skeletal Muscle","volume":"20","author":"Schnuck","year":"2016","journal-title":"J. Exerc. Nutr. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1042\/bst0311143","article-title":"Regulation of Pyruvate Dehydrogenase Complex Activity by Reversible Phosphorylation","volume":"31","author":"Holness","year":"2003","journal-title":"Biochem. Soc. Trans."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/6\/838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:10:26Z","timestamp":1760163026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/6\/838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,29]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["genes12060838"],"URL":"https:\/\/doi.org\/10.3390\/genes12060838","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,29]]}}}