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Effect of Mitotane on Male Gonadal Function

Federica Innocenti1, Sara Di Persio1, Marilena Taggi1

  • 1Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Sapienza University of Rome, 00185 Rome, Italy.

Cancers
|June 28, 2023
PubMed
Abstract

Insights

Mitotane (MTT) treatment for adrenocortical carcinoma causes testicular damage and reduces testosterone levels in male mice. This impacts sperm count and quality, affecting male reproductive health.

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.
Keywords:
adrenocortical carcinomamale gonadal functionmitotanetestistestosterone

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