{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:18:31Z","timestamp":1788995911817,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,18]],"date-time":"2023-06-18T00:00:00Z","timestamp":1687046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza Progetti di Ateneo 2020","award":["RM120172B957E7DB"],"award-info":[{"award-number":["RM120172B957E7DB"]}]},{"name":"Sapienza Progetti di Ateneo 2020","award":["MIUR Grant PRIN 2017 2017TK7Z8L"],"award-info":[{"award-number":["MIUR Grant PRIN 2017 2017TK7Z8L"]}]},{"name":"Ministry of Research","award":["RM120172B957E7DB"],"award-info":[{"award-number":["RM120172B957E7DB"]}]},{"name":"Ministry of Research","award":["MIUR Grant PRIN 2017 2017TK7Z8L"],"award-info":[{"award-number":["MIUR Grant PRIN 2017 2017TK7Z8L"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Clinical evidence has shown frequent hypogonadism following mitotane (MTT) treatment in male patients with adrenocortical carcinoma. This study aimed to evaluate the impact of MTT on male gonadal function. Methods: Morphological analysis of testes and testosterone assays were performed on adult CD1 MTT-treated and untreated mice. The expression of key genes involved in interstitial and tubular compartments was studied by real-time PCR. Moreover, quantitative and qualitative analysis of spermatozoa was performed. Results: Several degrees of damage to the testes and a significant testosterone reduction in MTT-treated mice were observed. A significant decline in 3\u03b2Hsd1 and Insl3 mRNA expression in the interstitial compartment confirmed an impairment of androgen production. Fsh-R mRNA expression was unaffected by MTT, proving that Sertoli cells are not the drug\u2019s primary target. Sperm concentrations were significantly lower in MTT-treated animals. Moreover, the drug caused a significant increase in the percentage of spermatozoa with abnormal chromatin structures. Conclusion: MTT negatively affects the male reproductive system, including changes in the morphology of testicular tissue and reductions in sperm concentration and quality.<\/jats:p>","DOI":"10.3390\/cancers15123234","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:59:51Z","timestamp":1687139991000},"page":"3234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Mitotane on Male Gonadal Function"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9842-5274","authenticated-orcid":false,"given":"Federica","family":"Innocenti","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Di Persio","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Taggi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Maggio","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pina","family":"Lardo","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Toscano","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3481-6908","authenticated-orcid":false,"given":"Rita","family":"Canipari","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-0145","authenticated-orcid":false,"given":"Elena","family":"Vicini","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7143-0775","authenticated-orcid":false,"given":"Antonio","family":"Stigliano","sequence":"additional","affiliation":[{"name":"Endocrinology, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.annonc.2020.08.2099","article-title":"Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Fassnacht","year":"2020","journal-title":"Ann. 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