Adverse Effects of High Concentrations of Fluoride on Characteristics of the Ovary and Mature Oocyte of Mouse

PLoS One. 2015 Jun 8;10(6):e0129594. doi: 10.1371/journal.pone.0129594. eCollection 2015.


Reproductive toxicity has been an exciting topic of research in reproductive biology in recent years. Soluble fluoride salts are toxic at high concentrations; their reproductive toxicity was assessed in this study by administering different fluoride salt concentrations to mice. Continuous feeding for five weeks resulted in damage to the histological architecture of ovaries. The expression of genes, including Dazl, Stra8, Nobox, Sohlh1, and ZP3 gene, associated with oocyte formation were much lower in the experimental group as compared with the control group. The number of in vitro fertilization of mature oocytes were also much lower in the experimental group as compared with control. Moreover, the fertility of female mice, as assessed by mating with normal male mice, was also lower in experimental compared with control groups. The expression of the oocyte-specific genes: Bmp15, Gdf9, H1oo, and ZP2, which are involved in oocyte growth and the induction of the acrosome reaction, decreased with the fluoride administration. DNA methylation and histone acetylation (H3K18ac and H3K9ac) are indispensable for germline development and genomic imprinting in mammals, and fluoride administration resulted in reduced levels of H3K9ac and H3K18ac in the experimental group as compared with the control group, as detected by immunostaining. Our results indicate that the administration of high concentrations of fluoride to female mice significantly reduced the number of mature oocytes and hampered their development and fertilization. Thus, this study lays a foundation for future studies on fluoride-induced reproductive disorders in women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Cell Differentiation / drug effects*
  • DNA Methylation / drug effects
  • Female
  • Fertilization in Vitro
  • Fluorides / administration & dosage
  • Fluorides / adverse effects*
  • Gene Expression Regulation / drug effects
  • Germ Cells / metabolism
  • Histones / metabolism
  • Male
  • Mice
  • Oocytes / drug effects*
  • Oocytes / metabolism
  • Ovary / drug effects*
  • Ovary / ultrastructure


  • Histones
  • Fluorides

Grant support

This work was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2011AA100303) (