{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:56:20Z","timestamp":1782924980147,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Throughout the reproductive life of women, cumulus cells (CC) protect the dormant oocyte from damage, act as sensors of the follicular microenvironment, and act as a gatekeeper for oocyte developmental potential. One such mechanism relies on the hypoxia\u2010tolerance response, which, with age, decreases systematically, including in the ovary. We aimed to evaluate the association between gene expression related to hypoxia and aging in CC and reproductive results in in vitro fertilization cycles. We recruited 94 women undergoing controlled ovarian stimulation. Total RNA was extracted from pooled CCs collected after oocyte pick\u2010up (OPU) and reverse\u2010transcribed to complementary DNA using random hexamers to test 14 genes related to hypoxia response via HIF1\u03b1 activation, oxidative stress, and angiogenic responses. The expression of\n                    <jats:italic>CLU<\/jats:italic>\n                    ,\n                    <jats:italic>NOS2<\/jats:italic>\n                    , and\n                    <jats:italic>TXNIP<\/jats:italic>\n                    had a positive correlation with age (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u20090.25,\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u20090.24, and\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u20090.35, respectively). Additionally,\n                    <jats:italic>NOS2<\/jats:italic>\n                    and\n                    <jats:italic>HMOX1<\/jats:italic>\n                    expression correlated positively with the retrieval of immature oocytes (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u20090.22 and\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u20090.40, respectively). Moreover,\n                    <jats:italic>VEGFC<\/jats:italic>\n                    levels decreased overall with increasing fertilization rate, independently of age (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u2009=\u2009\u22120.29). We found that the fertilization potential of a cohort of oocytes is related to the ability of CC to respond to oxidative stress and hypoxia with age, pointing at NOS2, HMOX1, and VEGFC expression as markers for oocyte maturation and fertilization success.\n                  <\/jats:p>","DOI":"10.1002\/mrd.23698","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T08:43:47Z","timestamp":1690188227000},"page":"369-377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The expression levels of\n                    <i>NOS2<\/i>\n                    ,\n                    <i>HMOX1<\/i>\n                    , and\n                    <i>VEGFC<\/i>\n                    in cumulus cells are markers of oocyte maturation and fertilization rate"],"prefix":"10.1002","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8859-6643","authenticated-orcid":false,"given":"Montserrat","family":"Barrag\u00e1n","sequence":"first","affiliation":[{"name":"EUGIN Group, Research and Development Parc Cient\u00edfic de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cornet\u2010Bartolom\u00e9","sequence":"additional","affiliation":[{"name":"EUGIN Group, Research and Development Parc Cient\u00edfic de Barcelona Barcelona Spain"},{"name":"Department of Genetics, Microbiology and Statistic, CIBERER, IBUB, IRSJD Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3578-316X","authenticated-orcid":false,"given":"Natalia","family":"Molina","sequence":"additional","affiliation":[{"name":"EUGIN Group, Research and Development Parc Cient\u00edfic de Barcelona Barcelona Spain"},{"name":"Universitat Pompeu Fabra Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0846-0365","authenticated-orcid":false,"given":"Rita","family":"Vassena","sequence":"additional","affiliation":[{"name":"EUGIN Group, Research and Development Parc Cient\u00edfic de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2004.6.924"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioab241"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719114525268"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu203"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153562"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/332459a0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/bjmg-2016-0001"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-020-01693-x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061396"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gan040"},{"key":"e_1_2_8_13_1","first-page":"109","volume-title":"Conn's handbook of models for human aging","author":"Duncan F. E.","year":"2018"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8100428"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a137570"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2010.12.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jmwh.12205"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-5193(66)90184-6"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-014-0113-3"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2012.01.023"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092389"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186287"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-20-0509"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(01)01854-4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.08.012"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1106"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmp014"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaw038"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab226"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(16)56933-7"},{"key":"e_1_2_8_31_1","unstructured":"Oliveros J. C.(2007\u20102015)Venny. An interactive tool for comparing lists with Venn's diagrams.https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.06.025"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.5653\/cerm.2021.04917"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.09.134"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2013.06.001"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2020.06.012"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116450"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.03.014"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_2_8_39_2","doi-asserted-by":"crossref","unstructured":"Erratum in:Nucleic Acids Research 2021Oct 11;49(18):10800.https:\/\/doi.org\/10.1093\/nar\/gkaa1074","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1042"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaa196"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.01.129"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-021-00704-5"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.064741"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/8.2.141"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008772"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gau031"}],"container-title":["Molecular Reproduction and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mrd.23698","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T10:25:14Z","timestamp":1692267914000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mrd.23698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/mrd.23698"],"URL":"https:\/\/doi.org\/10.1002\/mrd.23698","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.07.22.22277925","asserted-by":"object"}]},"ISSN":["1040-452X","1098-2795"],"issn-type":[{"value":"1040-452X","type":"print"},{"value":"1098-2795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6]]},"assertion":[{"value":"2022-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}