Influence of Onabotulinumtoxin A on testes of the growing rat

J Biochem Mol Toxicol. 2016 Dec;30(12):608-613. doi: 10.1002/jbt.21828. Epub 2016 Aug 5.

Abstract

Onabotulinumtoxin A (onabotA) is gaining wide medical use in children. The present study was planned to investigate the influence of its injection on the maturing testicular structures in rats. Immature rats were injected in the bilateral cremaster muscles by onabotA with three doses of (10, 20, and 40 U/kg) three times in a 2-week interval. The effect of these injections on fertility indices was examined. Levels of antisperm antibodies and several apoptosis parameters were also investigated. DNA content in form of ploidy and histopathological alterations were assessed. OnabotA-injected groups showed decreased sperm count and semen quality, while sperm vitality, morphology, and testosterone levels were not significantly affected. Furthermore, DNA flow cytometric analysis confirmed delayed sperm maturation. Apoptosis markers were significantly increased by the injections. In conclusion, onabotA injection in growing rats adversely affected sperm count and maturation. OnabotA testicular effects are mediated, at least partly, by apoptosis.

Keywords: Onabotulinumtoxin A. rats; apoptosis; spermatogenesis; testes.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Botulinum Toxins, Type A / pharmacology*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Gene Expression Regulation / drug effects*
  • Injections, Intramuscular
  • Male
  • Ploidies
  • Rats
  • Rats, Sprague-Dawley
  • Semen Analysis
  • Sexual Maturation / genetics
  • Sperm Motility / drug effects*
  • Spermatozoa / cytology
  • Spermatozoa / drug effects*
  • Spermatozoa / metabolism
  • Testis / cytology
  • Testis / drug effects*
  • Testis / metabolism
  • Testosterone / blood
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Bax protein, rat
  • Fas protein, rat
  • bcl-2-Associated X Protein
  • fas Receptor
  • Testosterone
  • Casp3 protein, rat
  • Caspase 3
  • Botulinum Toxins, Type A