{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:11:13Z","timestamp":1790802673066,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Oocyte developmental competence is one of the determining factors that influence the outcomes of an IVF cycle regarding the ability of a female gamete to reach maturation, be fertilized, and uphold an embryonic development up until the blastocyst stage. The current approach of assessing the competency of an oocyte is confined to an ambiguous and subjective oocyte morphological evaluation. Over the years, a myriad of biomarkers in the cumulus-oocyte-complex has been identified that could potentially function as molecular predictors for IVF program prognosis. This review aims to describe the predictive significance of several cumulus-oocyte complex (COC) biomarkers in evaluating oocyte developmental competence. A total of eight acclaimed cumulus biomarkers are examined in the study. RT-PCR and microarray analysis were extensively used to assess the significance of these biomarkers in foreseeing oocyte developmental competence. Notably, these biomarkers regulate vital processes associated with oocyte maturation and were found to be differentially expressed in COC encapsulating oocytes of different maturity. The biomarkers were reviewed according to the respective oocyte maturation events namely: nuclear maturation, apoptosis, and extracellular matrix remodeling, and steroid metabolism. Although substantial <jats:italic>in vitro<\/jats:italic> evidence was presented to justify the potential use of cumulus biomarkers in predicting oocyte competency and IVF outcomes, the feasibility of assessing these biomarkers as an add-on prognostic procedure in IVF is still restricted due to study challenges.<\/jats:p>","DOI":"10.3389\/fcell.2021.710292","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T14:56:00Z","timestamp":1630680960000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":49,"title":["Oocyte Competence Biomarkers Associated With Oocyte Maturation: A Review"],"prefix":"10.3389","volume":"9","author":[{"given":"Batara","family":"Sirait","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Budi","family":"Wiweko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Aulia","family":"Jusuf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dein","family":"Iftitah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Muharam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.mce.2013.07.027","article-title":"The regulation of maturation promoting factor during prophase I arrest and meiotic entry in mammalian oocytes.","volume":"382","author":"Adhikari","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008763","article-title":"Metabolic stress in autophagy and cell death pathways.","volume":"4","author":"Altman","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1083\/jcb.71.2.680","article-title":"Gap junctions between the oocyte and companion follicle cells in the mammalian ovary.","volume":"71","author":"Anderson","year":"1976","journal-title":"J. Cell. Biol."},{"key":"B4","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-1-4419-1780-5_13","article-title":"Assessment of oocyte quality","author":"Balaban","year":"2012","journal-title":"Practical Manual of in Vitro Fertilization"},{"key":"B5","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1002\/mrd.10239","article-title":"Serine protease inhibitor-E2 (SERPINE2) is differentially expressed in granulosa cells of dominant follicle in cattle.","volume":"64","author":"B\u00e9dard","year":"2003","journal-title":"Mol. Reprod. Dev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.fertnstert.2016.01.022","article-title":"Regimen of ovarian stimulation affects oocyte and therefore embryo quality.","volume":"105","author":"Bosch","year":"2016","journal-title":"Fertil. Steril."},{"key":"B7","first-page":"70","article-title":"Immature oocyte incidence: contributing factors and effects on mature sibling oocytes in intracytoplasmic sperm injection cycles.","volume":"24","author":"Braga","year":"2020","journal-title":"JBRA Assist. Reprod."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-14-32","article-title":"Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis.","volume":"14","author":"Brentnall","year":"2013","journal-title":"BMC Cell Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"52","DOI":"10.4236\/ojapo.2014.33006","article-title":"Clomiphene citrate induces ROS-mediated apoptosis in mammalian oocytes.","volume":"3","author":"Chaube","year":"2014","journal-title":"Open J. Apoptosis"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/213570","article-title":"High-throughput analysis of ovarian granulosa cell transcriptome.","volume":"2014","author":"Chronowska","year":"2014","journal-title":"Biomed Res. Int."},{"key":"B11","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.mce.2011.11.002","article-title":"Novel signaling mechanisms in the ovary during oocyte maturation and ovulation.","volume":"356","author":"Conti","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047106","article-title":"Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist.","volume":"7","author":"Devjak","year":"2012","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1095\/biolreprod.107.066019","article-title":"Meiotic arrest in human oocytes is maintained by a Gs signaling pathway.","volume":"78","author":"DiLuigi","year":"2008","journal-title":"Biol. Reprod."},{"key":"B14","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.mce.2006.03.009","article-title":"Meiotic arrest of oocytes depends on cell-to-cell communication in the ovarian follicle.","volume":"252","author":"Edry","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"B15","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.fertnstert.2009.11.039","article-title":"Metaphase II human oocyte morphology: contributing factors and effects on fertilization potential and embryo developmental ability in ICSI cycles.","volume":"94","author":"Figueira","year":"2010","journal-title":"Fertil. Steril."},{"key":"B16","article-title":"Controlled ovarian stimulation protocols for assisted reproduction: a network meta-analysis.","volume":"2017","author":"Gallos","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.anireprosci.2004.05.017","article-title":"Oocyte-somatic cell interactions during follicle development in mammals.","volume":"8","author":"Gilchrist","year":"2004","journal-title":"Anim. Reprod. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1083\/jcb.78.1.58","article-title":"Cell-to-cell communication and ovulation. A study of the cumulus-oocyte complex.","volume":"78","author":"Gilula","year":"1978","journal-title":"J. Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1016\/j.fertnstert.2011.03.045","article-title":"Influence of follicular fluid GDF9 and BMP15 on embryo quality.","volume":"95","author":"Gode","year":"2011","journal-title":"Fertil. Steril."},{"key":"B20","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s10815-007-9155-4","article-title":"Reduction of connexin 43 in human cumulus cells yields good embryo competence during ICSI.","volume":"24","author":"Hasegawa","year":"2007","journal-title":"J. Assist. Reprod. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1055\/s-2005-872451","article-title":"Oocyte maturation: the coming of age of a germ cell.","volume":"23","author":"Jamnongjit","year":"2005","journal-title":"Semin. Reprod. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.cbi.2015.01.008","article-title":"HSD17B1 expression enhances estrogen signaling stimulated by the low active estrone, evidenced by an estrogen responsive element-driven reporter gene in vivo.","volume":"234","author":"J\u00e4rvensivu","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"B23","doi-asserted-by":"crossref","first-page":"E1524","DOI":"10.1210\/jc.2012-1427","article-title":"LH-receptor gene expression in human granulosa and cumulus cells from antral and preovulatory follicles.","volume":"97","author":"Jeppesen","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1210\/en.2003-1051","article-title":"Luteinizing hormone-induced connexin 43 down-regulation: inhibition of translation.","volume":"145","author":"Kalma","year":"2004","journal-title":"Endocrinology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1007\/s10815-019-01489-8","article-title":"Cumulus cell pappalysin-1, luteinizing hormone\/choriogonadotropin receptor, amphiregulin and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 mRNA levels associate with oocyte developmental competence and embryo outcomes.","volume":"36","author":"Kordus","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1369\/jhc.3a6227.2004","article-title":"Gap junctional communication and connexin43 expression in relation to apoptotic cell death and survival of granulosa cells.","volume":"52","author":"Krysko","year":"2004","journal-title":"J. Histochem. Cytochem."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143632","article-title":"Oocyte scoring enhances embryo-scoring in predicting pregnancy chances with IVF where it counts most.","volume":"10","author":"Lazzaroni-Tealdi","year":"2015","journal-title":"PLoS One"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-015-0091-3","article-title":"Correlation of cumulus gene expression of GJA1, PRSS35, PTX3, and SERPINE2 with oocyte maturation, fertilization, and embryo development.","volume":"13","author":"Li","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-12-81","article-title":"Increased GDF9 and BMP15 mRNA levels in cumulus granulosa cells correlate with oocyte maturation, fertilization, and embryo quality in humans.","volume":"12","author":"Li","year":"2014","journal-title":"Reprod. Biol. Endocrinol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.fertnstert.2011.12.027","article-title":"High expression of luteinizing hormone receptors messenger RNA by human cumulus granulosa cells is in correlation with decreased fertilization.","volume":"97","author":"Maman","year":"2012","journal-title":"Fertil. Steril."},{"key":"B31","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s00404-016-4068-z","article-title":"Altered FoxO3 expression and apoptosis in granulosa cells of women with polycystic ovary syndrome.","volume":"294","author":"Mikaeili","year":"2016","journal-title":"Arch. Gynecol. Obstet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"24007","DOI":"10.1074\/jbc.m115.671487","article-title":"Cumulin, an oocyte-secreted heterodimer of the transforming growth factor-\u03b2 family, is a potent activator of granulosa cells and improves oocyte quality.","volume":"290","author":"Mottershead","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.1242\/dev.025494","article-title":"Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption.","volume":"135","author":"Norris","year":"2008","journal-title":"Development"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1242\/dev.035238","article-title":"Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte.","volume":"136","author":"Norris","year":"2009","journal-title":"Development"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1210\/en.2018-00485","article-title":"Coordination of ovulation and oocyte maturation: a good egg at the right time.","volume":"159","author":"Robker","year":"2018","journal-title":"Endocrinology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s10815-013-9943-y","article-title":"New molecular markers for the evaluation of gamete quality.","volume":"30","author":"Ruvolo","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1007\/s00404-017-4523-5","article-title":"Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome.","volume":"296","author":"Salehi","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"B38","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.fertnstert.2019.08.070","article-title":"Oocyte meiotic spindle morphology is a predictive marker of blastocyst ploidy\u2014a prospective cohort study.","volume":"113","author":"Tilia","year":"2020","journal-title":"Fertil. Steril."},{"key":"B39","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1530\/reprod\/122.4.619","article-title":"Involvement of connexin 43 in meiotic maturation of bovine oocytes.","volume":"122","author":"Vozzi","year":"2001","journal-title":"Reproduction"},{"key":"B40","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1111\/j.1582-4934.2008.00373.x","article-title":"Connexin expression and gap junctional coupling in human cumulus cells: contribution to embryo quality.","volume":"13","author":"Wang","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1071\/rd06103","article-title":"Evaluation of oocyte quality: morphological, cellular and molecular predictors.","volume":"19","author":"Wang","year":"2007","journal-title":"Reprod. Fertil. Dev."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.17036.1","article-title":"Correlation between luteinizing hormone receptor gene expression in human granulosa cells with oocyte quality in poor responder patients undergoing in vitro fertilization: a cross-sectional study.","volume":"8","author":"Wiweko","year":"2019","journal-title":"F1000Res."},{"key":"B43","doi-asserted-by":"crossref","DOI":"10.1186\/s13048-020-00696-7","article-title":"Transcriptomics of cumulus cells\u2013a window into oocyte maturation in humans.","volume":"13","author":"Wyse","year":"2020","journal-title":"J. Ovarian Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.mce.2010.07.019","article-title":"ADAMTS-1: a new human ovulatory gene and a cumulus marker for fertilization capacity.","volume":"328","author":"Yung","year":"2010","journal-title":"Mol. Cell. Endocrinol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.710292\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T14:56:08Z","timestamp":1630680968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.710292\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,30]]},"references-count":44,"alternative-id":["10.3389\/fcell.2021.710292"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.710292","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,30]]},"article-number":"710292"}}