Protective role of vitamin E in testicular development of mice exposed to valproic acid

Andrologia. 2021 Sep;53(8):e14140. doi: 10.1111/and.14140. Epub 2021 Jun 21.


Valproic acid (VPA) is a teratogenic antiepileptic, causing alterations in oxidative stress in prenatal development, being altered the development of the male reproductive system. The purpose of this study was to determine the protective effect of vitamin E (VE) on the testicular development in embryos, foetuses and pubertal mice exposed to VPA, VPA+VE and only VE. Sixty pregnant adult female mice were used, to which they were administered 600 mg/kg of VPA (VPA groups), 600 mg/kg of VPA and 200 IU of VE (VPA+VE groups), 200 IU VE (VE groups) and 0.3 ml of 0.9% physiological solution (control groups), showing at 12.5 days post-coital (dpc), 17.5 dpc and 6 weeks postnatal testicular development, and proliferative and apoptotic indices. The groups treated with VPA presented a smaller testicular volume, with greater interstitial space and a delay in the conformation of the testicular cords, shorter lengths and diameters of the germinal epithelium, a smaller number of germline and somatic cells, an increase in cells apoptotic and less proliferation, with significant differences. VE-treated groups behaved similarly to controls. In conclusion, VE reduces the effects caused by VPA throughout testicular development, from embryonic stages, continuing until pubertal stages.

Keywords: congenital malformations; spermatogenesis; testicular development; valproic acid; vitamin E.

MeSH terms

  • Animals
  • Anticonvulsants / toxicity
  • Female
  • Male
  • Mice
  • Oxidative Stress
  • Pregnancy
  • Testis
  • Valproic Acid* / toxicity
  • Vitamin E* / pharmacology


  • Anticonvulsants
  • Vitamin E
  • Valproic Acid