{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:02:37Z","timestamp":1793318557631,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,4,6]],"date-time":"2019-04-06T00:00:00Z","timestamp":1554508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1007027"],"award-info":[{"award-number":["1007027"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1016701"],"award-info":[{"award-number":["1016701"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1050130"],"award-info":[{"award-number":["1050130"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001026","name":"National Breast Cancer Foundation","doi-asserted-by":"publisher","award":["NC14-001"],"award-info":[{"award-number":["NC14-001"]}],"id":[{"id":"10.13039\/501100001026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It is well established that DNA-damaging chemotherapies can cause infertility and ovarian endocrine failure by depleting the ovarian reserve of primordial follicles. Currently, no effective pharmacological therapies exist for the preservation of long-term fertility and ovarian function in female cancer patients, due to a limited understanding of the mechanisms of chemotherapy-induced follicle depletion. This study investigated the cellular targets, molecular mechanisms, and temporal course of ovarian reserve depletion following treatment with commonly used chemotherapeutic drugs. Adult female C57BL\/6 mice were injected i.p. with saline, cisplatin (5mg\/kg), or cyclophosphamide (300mg\/kg); ovaries were harvested after 8 or 24 hours. Follicle counts showed depletion of all follicular stages 24 hours after administration of cisplatin or cyclophosphamide. Eight hours post-treatment, H2A histone family member X (\u03b3H2AX) immunofluorescence showed DNA double-stranded breaks at all follicular stages, including within primordial follicle oocytes. This staining was resolving by 24 hours, indicating that primordial follicle oocytes begin to undergo either apoptosis or repair in this timeframe. \u03b3H2AX-positive follicles were further examined to identify the specific cell types damaged. In primordial, transitional, and primary follicles, only oocytes sustained DNA damage, whereas in secondary and antral follicles, only somatic cells were affected. TUNEL staining confirmed that apoptosis occurs in these targeted cell types. Whilst multi-drug and multi-dose regimens were not examined, this study conclusively shows that cyclophosphamide and cisplatin cause direct damage to primordial follicle oocytes, which then undergo apoptosis. Therefore, future pharmacological strategies to prevent chemotherapy-induced infertility in females must specifically prevent primordial follicle oocyte death.<\/jats:p>","DOI":"10.1093\/molehr\/gaz020","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T08:38:37Z","timestamp":1553762317000},"page":"433-444","source":"Crossref","is-referenced-by-count":129,"title":["Cisplatin- and cyclophosphamide-induced primordial follicle depletion is caused by direct damage to oocytes"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5274-6291","authenticated-orcid":false,"given":"Q N","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, 3052, Australia"},{"name":"Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Zerafa","sequence":"additional","affiliation":[{"name":"Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S H","family":"Liew","sequence":"additional","affiliation":[{"name":"Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J K","family":"Findlay","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, 3052, Australia"},{"name":"Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, 3168, and Monash University, Clayton, 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Hickey","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, 3052, Australia"},{"name":"The Royal Women\u2019s Hospital, Parkville, 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K J","family":"Hutt","sequence":"additional","affiliation":[{"name":"Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,4,6]]},"reference":[{"key":"2019091013285628600_ref1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1080\/09553006214550391","article-title":"The radiosensitivity of germ-cells at various stages of ovarian 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