Sodium fluoride activates ERK and JNK via induction of oxidative stress to promote apoptosis and impairs ovarian function in rats

J Hazard Mater. 2014 May 15;272:75-82. doi: 10.1016/j.jhazmat.2014.03.011. Epub 2014 Mar 18.


The toxicity of sodium fluoride (NaF) to female fertility is currently recognized; however, the mechanisms are unclear. Previously, we reported a reduction in successful pregnancy rates, ovarian atrophy and dysfunction following exposure to NaF. The purpose of this study was to elucidate the underlying molecular mechanisms. Female Sprague-Dawley rats (10 rats/group) received 100 or 200mg/L NaF in their drinking water for 6 months or were assigned to an untreated control group. Apoptotic indices and oxidative stress indicators in blood and ovarian tissue were analyzed following sacrifice. The results confirmed the NaF-induced ovarian apoptosis, with concomitant activation of oxidative stress. Further investigations in ovarian granular cells showed that exposure to NaF activated extracellular regulated protein kinase (ERK) and c-Jun NH2 kinase (JNK), disrupting the ERK and JNK signaling pathways, while p38 and PI3K remained unchanged. These data demonstrated that oxidative stress may play a key role in NaF-induced ovarian dysfunction by activating the apoptotic ERK and JNK signaling pathways.

Keywords: Female reproduction; Ovarian apoptosis; Oxidative stress; Sodium fluoride.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Fertility / drug effects
  • MAP Kinase Kinase 4 / metabolism*
  • Ovary / drug effects*
  • Ovary / physiopathology
  • Oxidative Stress*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species
  • Sodium Fluoride / chemistry*


  • Reactive Oxygen Species
  • Sodium Fluoride
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase 4