Lower sperm quality and testicular and epididymal structural impairment in adult rats exposed to rosuvastatin during prepuberty

J Appl Toxicol. 2018 Jun;38(6):914-929. doi: 10.1002/jat.3599. Epub 2018 Feb 19.

Abstract

The increase of obesity, bad eating habits and the lack of physical exercises are highly related to dyslipidemias. Rosuvastatin is a lipid-lowering drug and has been indicated to prevent cardiovascular diseases and to treat dyslipidemias due to its higher efficiency to reduce serum cholesterol concentrations. This study aimed to evaluate the reproductive adverse effects on sexual maturity due to rosuvastatin exposure in juvenile male rats during prepuberty. Three groups were randomly formed with newly weaned rats: control, whose rats received saline solution 0.9% and rosuvastatin at doses of 3 or 10 mg kg-1 day-1 , administered orally by gavage, from postnatal day 21 until preputial separation (average of 45 days for controls and 49 days for statin-treated animals), indicative of puberty onset. Male rats were maintained until sexual maturity and were killed on postnatal day 110. In the rosuvastatin-treated groups, the results showed diminished follicle-stimulating hormone, luteinizing hormone and testosterone concentrations, increased estradiol and prolactin concentrations, histopathologic alterations on testis and epididymis and decreased sperm quality. Moreover, statin-exposed groups showed decreased expression of androgen receptor on testis and epididymis and lower expression of aquaporin-9 on epididymal epithelium. In conclusion, administration of rosuvastatin to prepubertal male rats provoked long-term hormonal deregulation and impaired reproduction at adulthood.

Keywords: Rosuvastatin; androgen; epididymis; male reproduction; testis; toxicology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Aquaporins / metabolism
  • Cell Proliferation / drug effects
  • Epididymis / drug effects*
  • Epididymis / metabolism
  • Epididymis / pathology
  • Hormones / blood
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / toxicity*
  • Male
  • Organ Size / drug effects
  • Rats, Wistar
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / metabolism
  • Reproduction / drug effects*
  • Rosuvastatin Calcium / toxicity*
  • Sexual Behavior, Animal / drug effects
  • Sexual Development / drug effects*
  • Sperm Count
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects*
  • Spermatozoa / metabolism
  • Spermatozoa / pathology
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology

Substances

  • Aqp9 protein, rat
  • Aquaporins
  • Hormones
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Receptors, Androgen
  • Rosuvastatin Calcium