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Effect of Mitotane on Male Gonadal Function.

Authors :
Innocenti F
Di Persio S
Taggi M
Maggio R
Lardo P
Toscano V
Canipari R
Vicini E
Stigliano A
Source :
Cancers [Cancers (Basel)] 2023 Jun 18; Vol. 15 (12). Date of Electronic Publication: 2023 Jun 18.
Publication Year :
2023

Abstract

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.<br />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.<br />Results: Several degrees of damage to the testes and a significant testosterone reduction in MTT-treated mice were observed. A significant decline in 3βHsd1 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's 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.<br />Conclusion: MTT negatively affects the male reproductive system, including changes in the morphology of testicular tissue and reductions in sperm concentration and quality.

Details

Language :
English
ISSN :
2072-6694
Volume :
15
Issue :
12
Database :
MEDLINE
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
37370841
Full Text :
https://doi.org/10.3390/cancers15123234