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

Abstract

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.

The regulation of trophoblast invasion and decidual reaction by matrix metalloproteinase‐2, metalloproteinase‐7, and metalloproteinase‐9 expressions in the rat endometrium

“…Numerous studies have indicated that matrix metalloproteinases (MMPs), such as MMP‐2, MMP‐7, MMP‐9, and TIMP‐1, which mediate the process of extracellular matrix (ECM) remodeling, play a critical role in cell migration progress, and are a prerequisite for angiogenesis 56‐60 . Reynolds and Redmer 61 indicated that the formation of new blood vessels is requisite for placentation and MMPs can contribute to angiogenesis.…”

Cadmium induces actin cytoskeleton alterations and dysfunction in Neuro‐2a cells

“…Proteins were electrophoresed and then transferred to PVDF membranes. Immune complexes were detected with horseradish peroxidase‐conjugated secondary antibody (CWBIO, China) and visualized by enhanced chemiluminescence (Pierce, Appleton, Wisconin) . Antibodies used included TAU (66499‐1‐lg, Proteintech, Chicago, Illinois), SYP (17785‐1‐AP, Proteintech), DBN (10260‐1‐AP, Proteintech), and GAPDH (bsm‐0978M, Proteintech).…”

“…Independent‐samples t test was performed using IBM SPSS Statistics 20.0 for parametric data. A P value of <0.05 was considered significant …”

Dietary High Sodium Fluoride Impairs Digestion and Absorption Ability, Mucosal Immunity, and Alters Cecum Microbial Community of Laying Hens

“…As we all know that F is necessary in lots of physiological activities. However, previous literatures have demonstrated that over-consumption of F not only damaged hard tissues, such as bone [3,4] and tooth [5,6], but also soft tissues, such as liver, kidney, thyroid, testis, uterus, and ovary [7][8][9][10][11]. Recently, literatures have suggested that over-intake F had intestinal toxicity [12,13], while the underlying mechanisms of the intestinal toxicity of F are unclear.…”