{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:11:08Z","timestamp":1790806268898,"version":"4.1.0"},"reference-count":21,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>\n                    Mitotane (MTT) is an adrenolytic drug used in advanced and adjuvant treatment of adrenocortical carcinoma, in Cushing\u2019s disease and in ectopic syndrome. However, knowledge about its effects on the ovary is still scarce. The purpose of this study is to investigate the effect of MTT on the ovary using\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    models. The study was performed in CD1 mice and in the COV-434 human ovarian granulosa cell line. We examined ovarian morphology, follicle development, steroidogenesis and procreative function in mice and the effect of MTT on cell growth\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Our results revealed that treatment of CD1 mice with MTT induces a decrease in early antral follicles with a subsequent increase in the secondary follicles, measured by the increased levels of anti-Mullerian Hormone (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05) and decreased levels of FSH receptor (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). Moreover, we observed a significant decrease in\n                    <jats:italic>Cyp11a1<\/jats:italic>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01) and\n                    <jats:italic>Cyp17a1<\/jats:italic>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) mRNA level in MTT-treated animals. Ovulation, induced by PMSG\/hCG stimulation, was also significantly impaired, with a reduction in the number of ovulated oocytes (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01) and fewer corpora lutea in treated animals. Likewise, the mating experiment demonstrated a delay in the time of conception as well as fewer pups per litter in MTT-treated mice (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). Experiments performed on the COV-434 cell line showed a significant inhibition of growth followed by apoptosis (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01). In conclusion, our study highlights the key points of ovarian folliculogenesis affected by MTT and demonstrates impairment of the ovulation process with a negative impact on conception, which is nevertheless preserved.\n                  <\/jats:p>","DOI":"10.1530\/joe-17-0203","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T20:10:19Z","timestamp":1493323819000},"page":"29-39","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":14,"title":["Effect of mitotane on mouse ovarian follicle development and fertility"],"prefix":"10.1530","volume":"234","author":[{"given":"Federica","family":"Innocenti","sequence":"first","affiliation":[{"name":"1DAHFMOUnit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Cerquetti","sequence":"additional","affiliation":[{"name":"2EndocrinologyDepartment of Clinical and Molecular Medicine, Sant\u2019Andrea Hospital, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Pezzilli","sequence":"additional","affiliation":[{"name":"2EndocrinologyDepartment of Clinical and Molecular Medicine, Sant\u2019Andrea Hospital, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Bucci","sequence":"additional","affiliation":[{"name":"3S. Pietro Hospital FatebenefratelliRome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Toscano","sequence":"additional","affiliation":[{"name":"2EndocrinologyDepartment of Clinical and Molecular Medicine, Sant\u2019Andrea Hospital, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Canipari","sequence":"additional","affiliation":[{"name":"1DAHFMOUnit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Stigliano","sequence":"additional","affiliation":[{"name":"2EndocrinologyDepartment of Clinical and Molecular Medicine, Sant\u2019Andrea Hospital, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2017062517101017000_234.1.29.1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0412"},{"key":"2017062517101017000_234.1.29.2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010915)92:6<1385::AID-CNCR1461>3.0.CO;2-2"},{"key":"2017062517101017000_234.1.29.3","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0358"},{"key":"2017062517101017000_234.1.29.4","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-53-4-672"},{"key":"2017062517101017000_234.1.29.5","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds231"},{"key":"2017062517101017000_234.1.29.6","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1210\/jc.2015-2341","article-title":"Pregnancy in women previously treated for an adrenocortical carcinoma","volume":"100","author":"de Corbiere","year":"2015","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2017062517101017000_234.1.29.7","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1240601"},{"key":"2017062517101017000_234.1.29.8","doi-asserted-by":"publisher","DOI":"10.1210\/er.2013-1029"},{"key":"2017062517101017000_234.1.29.9","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.235"},{"key":"2017062517101017000_234.1.29.10","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22361"},{"key":"2017062517101017000_234.1.29.11","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2281"},{"key":"2017062517101017000_234.1.29.12","doi-asserted-by":"publisher","DOI":"10.1159\/000341830"},{"key":"2017062517101017000_234.1.29.13","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3892\/mmr.2012.1244","article-title":"The effect of mitotane on viability, steroidogenesis and gene expression in NCIH295R adrenocortical cells","volume":"7","author":"Lehmann","year":"2013","journal-title":"Molecular Medicine Reports"},{"key":"2017062517101017000_234.1.29.14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2361"},{"key":"2017062517101017000_234.1.29.15","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-13-0150"},{"key":"2017062517101017000_234.1.29.16","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-0670"},{"key":"2017062517101017000_234.1.29.17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2374"},{"key":"2017062517101017000_234.1.29.18","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-07-0003"},{"key":"2017062517101017000_234.1.29.19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s40618-015-0349-9","article-title":"Management of adrenocortical carcinoma: a consensus statement of the Italian Society of Endocrinology (SIE)","volume":"39","author":"Stigliano","year":"2016","journal-title":"Journal of Endocrinological Investigation"},{"key":"2017062517101017000_234.1.29.20","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(78)90015-8"},{"key":"2017062517101017000_234.1.29.21","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2839"}],"container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/234\/1\/29.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/234\/1\/29.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:59Z","timestamp":1784555759000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/234\/1\/29-39\/8291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7]]},"references-count":21,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/joe-17-0203","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7]]}}}