Chronic fluoride exposure-induced testicular toxicity is associated with inflammatory response in mice

Chemosphere. 2016 Jun;153:419-25. doi: 10.1016/j.chemosphere.2016.03.045. Epub 2016 Mar 28.


Previous studies have indicated that fluoride (F) can affect testicular toxicity in humans and rodents. However, the mechanism underlying F-induced testicular toxicity is not well understood. This study was conducted to evaluate the sperm quality, testicular histomorphology and inflammatory response in mice followed F exposure. Healthy male mice were randomly divided into four groups with sodium fluoride (NaF) at 0, 25, 50, 100 mg/L in the drinking water for 180 days. At the end of the exposure, significantly increased percentage of spermatozoa abnormality was found in mice exposed to 50 and 100 mg/L NaF. Disorganized spermatogenic cells, vacuoles in seminiferous tubules and loss and shedding of sperm cells were also observed in the NaF treated group. In addition, chronic F exposure increased testicular interleukin-17(IL-17), interleukin-17 receptor C (IL-17RC), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in transcriptional levels, as well as IL-17 and TNF-α levels in translational levels. Interestingly, we observed that F treated group elevated testicular inducible nitric oxide synthase (iNOS) mRNA level and nitric oxide (NO) concentration. Taken together, these results indicated that testicular inflammatory response could contribute to chronic F exposure induced testicular toxicity in mice.

Keywords: Fluoride; Inflammatory response; Mice; Sperm; Testis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / toxicity*
  • Male
  • Mice
  • Nitric Oxide / metabolism*
  • Sodium Fluoride / toxicity*
  • Spermatozoa / drug effects*
  • Spermatozoa / physiology
  • Testis / anatomy & histology
  • Testis / drug effects*


  • Cytokines
  • Environmental Pollutants
  • Nitric Oxide
  • Sodium Fluoride