{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:21Z","timestamp":1787013981858,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003382","name":"Core Research for Evolutional Science and Technology","doi-asserted-by":"publisher","award":["JPMJCR19H4"],"award-info":[{"award-number":["JPMJCR19H4"]}],"id":[{"id":"10.13039\/501100003382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16H06276 [AdAMS (Aa210038)]"],"award-info":[{"award-number":["JP16H06276 [AdAMS (Aa210038)]"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19H05462 JP20H05502"],"award-info":[{"award-number":["JP19H05462 JP20H05502"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>BRCA1<\/jats:italic>\n                    is one of the causative genes for hereditary breast and ovarian cancer syndrome with a high risk of early\u2010onset breast cancer. Whereas olaparib (OLA), an inhibitor of poly\u2010ADP\u2010ribose polymerase, has been applied as adjuvant therapy to those cancer patients, its effect on ovarian reproductive function remains unelucidated. Recently, a rat model (MUT;\n                    <jats:italic>Brca1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>(L63X\/+)<\/jats:italic>\n                    <\/jats:sup>\n                    mutation) mimicking a human\n                    <jats:italic>BRCA1<\/jats:italic>\n                    pathogenic variant has been established. Using this model, we evaluated the effects of OLA on ovarian reproductive function in comparison with the wild\u2010type (WT) rats. MUT showed a significantly reduced number of primordial follicles and subfertility in accordance with aging. Oxidative stress was significantly elevated in the young MUT granulosa cells (GCs) accompanied by increased mTOR but decreased PTEN signals. OLA administration in MUT further decreased primordial follicles, with gene set enrichment analysis, indicating upregulated DNA repair pathways. Furthermore, a combination of OLA and cyclophosphamide (CPA) induced empty primordial follicles, recognized as CPA\u2010induced severe ovarian toxicity. Whereas OLA\u2009+\u2009CPA caused greater reduction in primordial follicles both in MUT and WT in comparison with CPA alone, MUT ovaries were more susceptible to oxidative stress, potentially depleting primordial follicles via activation of GCs and inducing oocyte death due to accumulated DNA damage by OLA treatment. Our findings in this preclinical model underscore the importance of evaluating ovarian reserve prior to chemotherapy by performing reproductive consultation with female patients with\n                    <jats:italic>BRCA1<\/jats:italic>\n                    pathogenic variants.\n                  <\/jats:p>","DOI":"10.1111\/cas.16412","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T01:40:17Z","timestamp":1738633217000},"page":"1139-1152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Susceptibility of\n                    <i>Brca1<\/i>\n                    <sup>\n                      (\n                      <i>L63X\/+<\/i>\n                      )\n                    <\/sup>\n                    rat to ovarian reserve dissipation by chemotherapeutic agents to breast cancer"],"prefix":"10.1111","volume":"116","author":[{"given":"Satoshi","family":"Kaseki","sequence":"first","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Sonehara","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4230-7559","authenticated-orcid":false,"given":"Yashiro","family":"Motooka","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Maternal and Perinatal Medicine Nagoya University Hospital  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Osuka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Akatsuka","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-1825","authenticated-orcid":false,"given":"Hiroaki","family":"Kajiyama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoji","family":"Mashimo","sequence":"additional","affiliation":[{"name":"Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science The University of Tokyo  Tokyo Japan"},{"name":"Division of Genome Engineering, Center for Experimental Medicine and Systems Biology, Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1507-585X","authenticated-orcid":false,"given":"Tatsuhiko","family":"Imaoka","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research Institute for Radiological Science, National Institutes for Quantum Science and Technology  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-1109","authenticated-orcid":false,"given":"Shinya","family":"Toyokuni","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Center for Low\u2010temperature Plasma Sciences Nagoya University  Nagoya Japan"},{"name":"Center for Integrated Sciences of Low\u2010temperature Plasma Core Research (iPlasma Core) Tokai National Higher Education and Research System  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.72"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21637"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12282-013-0503-1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.0476"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmz043"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.12.004"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004925"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24638"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-006-9220-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.08.014"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02880"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.01.033"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719117728800"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-017-1014-3"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127363"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60892-6"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2105215"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74087-9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.334425.119"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.12.006"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15485"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623315570339"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-016-9807-0"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1228088"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021010995"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092177"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2022.04.019"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2018.06.011"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719107312037"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010200"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00033-6"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102175"},{"key":"e_1_2_11_34_1","first-page":"365","article-title":"Quantitative immunohistochemical determination of 8\u2010hydroxy\u20102\u2032\u2010deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate\u2010induced renal carcinogenesis model","volume":"76","author":"Toyokuni S","year":"1997","journal-title":"Lab Investig"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101726"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2024.2320405"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioac099"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10173892"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800352115"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0860"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114028"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05859-0"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102356"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101616"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0633-7"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaz020"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706450"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.16412","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.16412","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T22:49:48Z","timestamp":1743806988000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.16412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,3]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/cas.16412"],"URL":"https:\/\/doi.org\/10.1111\/cas.16412","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,3]]},"assertion":[{"value":"2024-09-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}