Biological Trace Element Research

, Volume 178, Issue 2, pp 253–260 | Cite as

The MMP-9/TIMP-1 System is Involved in Fluoride-Induced Reproductive Dysfunctions in Female Mice

  • Hong-wei WangEmail author
  • Wen-peng Zhao
  • Pan-pan Tan
  • Jing Liu
  • Jing Zhao
  • Bian-hua Zhou


A total of 84 healthy female mice were kept with various concentrations of sodium fluoride (F) (0, 50, 100, 150 mg F/L in drinking water for 90 days) and were then mated with healthy male mice for 1 week to study the effect of excessive fluoride on female reproductive function, particularly in embryo implantation. The rate of pregnancy, litter size, and the birth weight of female mice were evaluated. Ultrastructural changes of uteri tissues were observed by transmission electron microscopy (TEM). The mRNA expression levels of MMP-9 and TIMP-1 were determined by quantitative real-time PCR. The protein expression levels of MMP-9 and TIMP-1 were analyzed by western blotting. Results showed a significant decrease of litter size in mice exposed to fluoride. TEM images of uteri tissue of mice that underwent a 150 mg/L F treatment for 90 days showed a vague nucleus, reduced microvilli, increased lysosomes, a dilated endoplasmic reticulum, and a vacuolization mitochondrion when compared with the control group. Following the damage of the structure, the expression levels of MMP-9 and TIMP-1 in uteri tissues were significantly unregulated in the F 150 group. These results show that MMP-9/TIMP-1 system disturbance and changes of histological structure in uteri tissue are involved in fluoride-induced reproductive dysfunctions.


Fluoride MMP-9 TIMP-1 Embryo implantation Uterus Female mice 



This work is sponsored by the China National Natural Science Foundation (grant no. 31201963).


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Hong-wei Wang
    • 1
    • 2
    Email author
  • Wen-peng Zhao
    • 1
  • Pan-pan Tan
    • 1
  • Jing Liu
    • 1
  • Jing Zhao
    • 1
  • Bian-hua Zhou
    • 1
  1. 1.Henan Provincial Open Laboratory of Key Disciplines, Environment and Animal Products Safety, College of Animal Science and TechnologyHenan University of Science and TechnologyLuoyangPeople’s Republic of China
  2. 2.College of Animal Science and TechnologyHenan University of Science and TechnologyLuoyangPeople’s Republic of China

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