Toxic effects of sodium fluoride on cell proliferation and apoptosis of Leydig cells from young mice

J Physiol Biochem. 2014 Sep;70(3):761-8. doi: 10.1007/s13105-014-0344-1. Epub 2014 Jul 30.


The biological effects of fluoride on human health are often extensive, either beneficial or detrimental. Among the various effects of fluoride exposure in different organs, the reproductive tract is particularly susceptible to disruption by fluoride at a sufficient concentration. It has attracted much attention to the effect of sodium fluoride on male fertility, gestational female, and offspring. Herein, we applied a widespread natural compound sodium fluoride (NaF) and investigated the effects of acute NaF exposure on Leydig cells, including their proliferation, apoptosis, and signal pathway changes. Our results demonstrated that high dosage of NaF could inhibit cell proliferation by stress-induced apoptosis, which was confirmed by cellular and molecular evidences. We found that fluoride exposure affected the expression levels of stress response factors, signal transduction components, and apoptosis-related proteins, including caspase-3/caspase-9, B-cell lymphoma 2 (Bcl-2), and Bax. This study suggests that the complex effects of fluoride on Leydig cells are closely related to its dosage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism
  • Leydig Cells / pathology
  • Male
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects
  • Sodium Fluoride / administration & dosage
  • Sodium Fluoride / toxicity*
  • bcl-2-Associated X Protein / metabolism


  • Bax protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Sodium Fluoride
  • Casp3 protein, mouse
  • Casp9 protein, mouse
  • Caspase 3
  • Caspase 9