{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T22:07:14Z","timestamp":1764194834957,"version":"3.37.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01HD096042-02"],"award-info":[{"award-number":["5R01HD096042-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cisplatin, a platinum-containing alkylating agent, is used in the treatment of various tumors owing to its potent antitumor activity. However, it causes permanent and adverse effects, particularly hearing loss and depletion of ovarian reserve. Until recently, there were no clinically available protective agents to mitigate the adverse side effects of cisplatin-induced cytotoxicity. In 2022, sodium thiosulfate (STS) was approved by the Food and Drug Administration for mitigating hearing loss in children and adolescents undergoing cisplatin treatment. Consequently, our investigation aimed to determine if STS could protect ovarian reserve against cisplatin-induced gonadotoxicity. In an ex vivo culture, the cisplatin-only group exhibited a loss of primordial follicles, while post-STS administration after cisplatin exposure effectively protected primordial follicles. However, when post-STS was administrated either 6 or 4\u00a0h after cisplatin exposure, it did not confer protection against cisplatin-induced gonadotoxicity in postnatal day 7 or adolescent mouse models. Immunofluorescence assays using \u03b3H2AX and cPARP revealed that oocytes within primordial follicles exhibited DNA damage after cisplatin exposure, irrespective of post-STS administration. This underscores the rapid and heightened sensitivity of oocytes to gonadotoxicity. In addition, oocytes demonstrated an increased expression of pCHK2 rather than pERK, suggesting that the pathway leading to oocyte death differs from the pathway observed in the inner ear cell death following cisplatin exposure. These results imply that while the administration of STS after cisplatin is highly beneficial in preventing hearing loss, it does not confer a protective effect on the ovaries in mouse models.<\/jats:p>","DOI":"10.1093\/biolre\/ioae003","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T02:17:05Z","timestamp":1704853025000},"page":"772-781","source":"Crossref","is-referenced-by-count":3,"title":["Sodium thiosulfate does not protect ovarian reserve from cisplatin-induced gonadotoxicity"],"prefix":"10.1093","volume":"110","author":[{"given":"Wonmi","family":"So","sequence":"first","affiliation":[{"name":"Olson Center for Women\u2019s Health , Department of Obstetrics and Gynecology, College of Medicine, , Omaha, NE , USA"},{"name":"University of Nebraska Medical Center , Department of Obstetrics and Gynecology, College of Medicine, , Omaha, NE , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amirhossein","family":"Abazarikia","sequence":"additional","affiliation":[{"name":"Olson Center for Women\u2019s Health , Department of Obstetrics and Gynecology, College of Medicine, , Omaha, NE , USA"},{"name":"University of Nebraska Medical Center , Department of Obstetrics and Gynecology, College of Medicine, , Omaha, NE , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary B","family":"Zelinski","sequence":"additional","affiliation":[{"name":"Division of Reproductive & Developmental Sciences , Oregon National Primate Research Center, , Beaverton, OR , USA"},{"name":"Oregon Health & Science University , Oregon National Primate Research Center, , Beaverton, OR , USA"},{"name":"Department of Obstetrics and Gynecology, School of Medicine, Oregon Health & Science University , Portland, OR , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So-Youn","family":"Kim","sequence":"additional","affiliation":[{"name":"Olson Center for Women\u2019s Health , Department of Obstetrics and Gynecology, College of Medicine, , Omaha, NE , USA"},{"name":"University of Nebraska Medical Center , Department of Obstetrics and Gynecology, College of Medicine, , Omaha, NE , USA"},{"name":"Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center , Omaha, NE , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"2024041508365524500_ref1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1188\/18.CJON.175-183","article-title":"Nephrotoxicity: evidence in patients receiving cisplatin therapy","volume":"22","author":"Duffy","year":"2018","journal-title":"Clin J Oncol Nurs"},{"key":"2024041508365524500_ref2","doi-asserted-by":"crossref","first-page":"13885","DOI":"10.1096\/fj.202001461RR","article-title":"Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation","volume":"34","author":"Eldani","year":"2020","journal-title":"FASEB J"},{"key":"2024041508365524500_ref3","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.1200\/JCO.2000.18.22.3819","article-title":"Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach\u2014results of the first prospective study of the International Society of Pediatric Oncology","volume":"18","author":"Pritchard","year":"2000","journal-title":"J Clin Oncol"},{"key":"2024041508365524500_ref4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1620\/tjem.219.177","article-title":"Cisplatin ototoxicity and protection: clinical and experimental studies","volume":"219","author":"Rybak","year":"2009","journal-title":"Tohoku J Exp Med"},{"key":"2024041508365524500_ref5","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1081\/CNV-200055951","article-title":"Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late effects surveillance system","volume":"23","author":"Stohr","year":"2005","journal-title":"Cancer Invest"},{"key":"2024041508365524500_ref6","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0022-3476(85)80098-6","article-title":"Renal toxicity of cisplatin in children","volume":"106","author":"Womer","year":"1985","journal-title":"J Pediatr"},{"key":"2024041508365524500_ref7","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/s41598-020-80853-6","article-title":"Combination therapy of cisplatin with cilastatin enables an increased dose of cisplatin, enhancing its antitumor effect by suppression of nephrotoxicity","volume":"11","author":"Arita","year":"2021","journal-title":"Sci Rep"},{"key":"2024041508365524500_ref8","first-page":"73","article-title":"High-dose cisplatin therapy using mannitol versus furosemide diuresis: comparative pharmacokinetics and toxicity","volume":"65","author":"Ostrow","year":"1981","journal-title":"Cancer Treat Rep"},{"key":"2024041508365524500_ref9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1186\/s12885-022-09456-w","article-title":"The effect of mannitol addition to hydration on acute kidney injury event after high dose cisplatin chemotherapy: an ambispective cohort study","volume":"22","author":"Rachman","year":"2022","journal-title":"BMC Cancer"},{"key":"2024041508365524500_ref10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00280-003-0620-1","article-title":"Saline, mannitol, and furosemide hydration in acute cisplatin nephrotoxicity: a randomized trial","volume":"52","author":"Santoso","year":"2003","journal-title":"Cancer Chemother Pharmacol"},{"key":"2024041508365524500_ref11","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1177\/019459989110400122","article-title":"The \"plateau effect\" of cis-platinum-induced hearing loss","volume":"104","author":"Myers","year":"1991","journal-title":"Otolaryngol Head Neck Surg"},{"key":"2024041508365524500_ref12","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/cncr.33848","article-title":"The cumulative incidence of cisplatin-induced hearing loss in young children is higher and develops at an early stage during therapy compared with older children based on 2052 audiological assessments","volume":"128","author":"Meijer","year":"2022","journal-title":"Cancer"},{"key":"2024041508365524500_ref13","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1124\/jpet.105.087601","article-title":"Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium thiosulfate as assessed at the molecular, cellular, and in vivo levels","volume":"314","author":"Dickey","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"key":"2024041508365524500_ref14","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1158\/1078-0432.CCR-06-2289","article-title":"Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity","volume":"14","author":"Harned","year":"2008","journal-title":"Clin Cancer Res"},{"key":"2024041508365524500_ref15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1054\/jcms.2002.0280","article-title":"In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human tongue and oesophageal squamous carcinoma cell lines","volume":"30","author":"Kovacs","year":"2002","journal-title":"J Craniomaxillofac Surg"},{"key":"2024041508365524500_ref16","first-page":"309","article-title":"Delayed administration of sodium thiosulfate in animal models reduces platinum ototoxicity without reduction of antitumor activity","volume":"6","author":"Muldoon","year":"2000","journal-title":"Clin Cancer Res"},{"key":"2024041508365524500_ref17","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1023\/A:1008296202198","article-title":"Experience with intraperitoneal cisplatin and etoposide and i.v. sodium thiosulphate protection in ovarian cancer patients with either pathologically complete response or minimal residual disease","volume":"8","author":"Rijswijk","year":"1997","journal-title":"Ann Oncol"},{"key":"2024041508365524500_ref18","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1056\/NEJMoa1801109","article-title":"Sodium thiosulfate for protection from cisplatin-induced hearing loss","volume":"378","author":"Brock","year":"2018","journal-title":"N Engl J Med"},{"key":"2024041508365524500_ref19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S1470-2045(16)30625-8","article-title":"Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial","volume":"18","author":"Freyer","year":"2017","journal-title":"Lancet Oncol"},{"key":"2024041508365524500_ref20","first-page":"23","article-title":"Drug approved to prevent cisplatin-associated ototoxicity in children","volume":"123","author":"Aschenbrenner","year":"2023","journal-title":"Am J Nurs"},{"key":"2024041508365524500_ref21","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1210\/er.2018-00092","article-title":"Long-term endocrine and metabolic consequences of cancer treatment: a systematic review","volume":"40","author":"Gebauer","year":"2019","journal-title":"Endocr Rev"},{"key":"2024041508365524500_ref22","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1210\/jc.2003-030352","article-title":"Reduced ovarian function in long-term survivors of radiation- and chemotherapy-treated childhood cancer","volume":"88","author":"Larsen","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2024041508365524500_ref23","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1007\/s00404-022-06538-9","article-title":"Protective effect of edaravone on cisplatin-induced injury in rat ovary","volume":"306","author":"Kara","year":"2022","journal-title":"Arch Gynecol Obstet"},{"key":"2024041508365524500_ref24","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/cdd.2013.31","article-title":"Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network","volume":"20","author":"Kim","year":"2013","journal-title":"Cell Death Differ"},{"key":"2024041508365524500_ref25","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41418-018-0151-2","article-title":"Transient inhibition of p53 homologs protects ovarian function from two distinct apoptotic pathways triggered by anticancer therapies","volume":"26","author":"Kim","year":"2019","journal-title":"Cell Death Differ"},{"key":"2024041508365524500_ref26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41594-018-0035-7","article-title":"Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63","volume":"25","author":"Tuppi","year":"2018","journal-title":"Nat Struct Mol Biol"},{"key":"2024041508365524500_ref27","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1210\/en.2014-1926","article-title":"Cell autonomous phosphoinositide 3-kinase activation in oocytes disrupts normal ovarian function through promoting survival and overgrowth of ovarian follicles","volume":"156","author":"Kim","year":"2015","journal-title":"Endocrinology"},{"key":"2024041508365524500_ref28","doi-asserted-by":"crossref","first-page":"9585","DOI":"10.1073\/pnas.160274797","article-title":"The human VASA gene is specifically expressed in the germ cell lineage","volume":"97","author":"Castrillon","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024041508365524500_ref29","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1126\/sciadv.abd0561","article-title":"BRAF inhibition protects against hearing loss in mice","volume":"6","author":"Ingersoll","year":"2020","journal-title":"Sci Adv"},{"key":"2024041508365524500_ref30","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/clinchem\/32.4.641","article-title":"Interaction of cisplatin and carboplatin with sodium thiosulfate: reaction rates and protein binding","volume":"32","author":"Elferink","year":"1986","journal-title":"Clin Chem"},{"key":"2024041508365524500_ref31","first-page":"1367","article-title":"\"Two-route chemotherapy\" using high-dose ip cisplatin and iv sodium thiosulfate, its antidote, for peritoneally disseminated cancer in mice","volume":"68","author":"Iwamoto","year":"1984","journal-title":"Cancer Treat Rep"},{"key":"2024041508365524500_ref32","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1039\/C6MT00183A","article-title":"Tuning the metabolism of the anticancer drug cisplatin with chemoprotective agents to improve its safety and efficacy","volume":"8","author":"Sooriyaarachchi","year":"2016","journal-title":"Metallomics"},{"key":"2024041508365524500_ref33","doi-asserted-by":"crossref","first-page":"H256","DOI":"10.1152\/ajpheart.00723.2016","article-title":"Role of thiosulfate in hydrogen sulfide-dependent redox signaling in endothelial cells","volume":"313","author":"Leskova","year":"2017","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2024041508365524500_ref34","doi-asserted-by":"crossref","first-page":"333","DOI":"10.4103\/2221-1691.284948","article-title":"Anti-proliferative potential of sodium thiosulfate against HT 29 human colon cancer cells with augmented effect in the presence of mitochondrial electron transport chain inhibitors","volume":"10","author":"Sivakumar","year":"2020","journal-title":"Asian Pac J Trop Biomed"},{"key":"2024041508365524500_ref35","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1080\/15384101.2014.995496","article-title":"New strategy for in vitro activation of primordial follicles with mTOR and PI3K stimulators","volume":"14","author":"Sun","year":"2015","journal-title":"Cell Cycle"},{"key":"2024041508365524500_ref36","doi-asserted-by":"crossref","first-page":"10280","DOI":"10.1073\/pnas.1001198107","article-title":"Activation of dormant ovarian follicles to generate mature eggs","volume":"107","author":"Li","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024041508365524500_ref37","first-page":"119","article-title":"New insights into the role of phosphoinositide 3-kinase activity in the physiology of immature oocytes: lessons from recent mouse model studies","volume":"3","author":"Kim","year":"2018","journal-title":"Eur Med J Reprod Health"},{"key":"2024041508365524500_ref38","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.mce.2011.05.027","article-title":"Functional roles of the phosphatidylinositol 3-kinases (PI3Ks) signaling in the mammalian ovary","volume":"356","author":"Zheng","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"2024041508365524500_ref39","first-page":"6297","article-title":"Comparative pharmacokinetics of cisplatin and three analogues in mice and humans","volume":"47","author":"Hennik","year":"1987","journal-title":"Cancer Res"},{"key":"2024041508365524500_ref40","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s10557-017-6751-0","article-title":"Sodium thiosulfate preconditioning ameliorates ischemia\/reperfusion injury in rat hearts via reduction of oxidative stress and apoptosis","volume":"31","author":"Ravindran","year":"2017","journal-title":"Cardiovasc Drugs Ther"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioae003\/56409672\/ioae003.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/110\/4\/772\/57214474\/ioae003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/110\/4\/772\/57214474\/ioae003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T08:38:00Z","timestamp":1713170280000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/110\/4\/772\/7513636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,9]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,1,9]]},"published-print":{"date-parts":[[2024,4,11]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioae003","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"type":"print","value":"0006-3363"},{"type":"electronic","value":"1529-7268"}],"subject":[],"published-other":{"date-parts":[[2024,4]]},"published":{"date-parts":[[2024,1,9]]}}}