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As improved treatment options increase cancer survival, it has become increasingly important to address fertility issues in cancer survivors. In this study, we examined the pathophysiological effects of multiple exposures to cyclophosphamide (Cy) on the ovaries of mice and their underlying molecular mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female C57BL\/6 mice were intraperitoneally injected with 100\u2009mg\/kg Cy six times over 2\u2009weeks; 4\u2009weeks later, the mice were sacrificed and their ovaries, sera, and oocytes were collected for histological observation, measurement of anti-M\u00fcllerian hormone levels, and assessment of oocyte quantity and quality in response to hormonal stimulation. Gene expression changes in Cy-treated ovaries were examined by microarray and bioinformatics analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After repeated Cy exposure, the anti-M\u00fcllerian hormone level was decreased, and follicle loss and impairments in the quality of oocyte were irreversible. The expression levels of genes involved in folliculogenesis, oogenesis, and zona pellucida glycoprotein transcription displayed sustained alterations in Cy-exposed ovaries even after 4\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The adverse effects of Cy on ovarian function and oocytes remained even after chemotherapy was complete. Therefore, strategies to prevent ovarian damage or restore ovarian function after treatment are required to safeguard the fertility of young cancer survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-020-00468-5","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T13:04:01Z","timestamp":1610024641000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Extended adverse effects of cyclophosphamide on mouse ovarian function"],"prefix":"10.1186","volume":"22","author":[{"given":"Jihyun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6948-892X","authenticated-orcid":false,"given":"Sooseong","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"issue":"509","key":"468_CR1","doi-asserted-by":"publisher","first-page":"eaaw8412","DOI":"10.1126\/scitranslmed.aaw8412","volume":"11","author":"A Lin","year":"2019","unstructured":"Lin A, Giuliano CJ, Palladino A, John KM, Abramowicz C, Yuan ML, Sausville EL, Lukow DA, Liu L, Chait AR, Galluzzo ZC, Tucker C, Sheltzer JM. 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Experimental animal protocols were approved by the Institutional Animal Care and Use Committee at Korea Institute of Oriental Medicine (19\u2013019, Daejeon, Korea). No permission was necessary to collect the specimens in our study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"I understand that the text and any pictures published in the article will be freely available on the internet and may be seen by the general public. I have been offered the opportunity to read the manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3"}}