Effect of Mitotane on Male Gonadal Function.

Area of Science:

• Endocrinology
• Reproductive Biology
• Toxicology

Background:

• Adrenocortical carcinoma treatment with mitotane (MTT) is associated with hypogonadism in male patients.
• The precise impact of MTT on male gonadal function requires further investigation.

Purpose of the Study:

• To evaluate the effects of mitotane (MTT) on male reproductive system function in a preclinical model.
• To assess testicular morphology, hormone levels, gene expression, and sperm parameters following MTT exposure.

Main Methods:

• Adult male CD1 mice were treated with MTT or a placebo.
• Testicular histology, serum testosterone levels, key gene expression (real-time PCR), and sperm analysis were performed.
• Quantitative and qualitative sperm parameters, including chromatin structure, were assessed.

Main Results:

• MTT induced testicular damage and significantly reduced testosterone levels.
• Impaired androgen production was indicated by decreased 3βHsd1 and Insl3 mRNA expression.
• Sperm concentration decreased, and the percentage of spermatozoa with abnormal chromatin structures increased significantly.

Conclusions:

• Mitotane (MTT) adversely affects the male reproductive system.
• MTT treatment leads to testicular tissue damage, reduced sperm concentration, and impaired sperm quality.