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基质金属蛋白酶-9/金属蛋白酶组织抑制因子-1系统参与氟诱导的雌性小鼠生殖功能障碍。

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

作者信息

Wang Hong-Wei, Zhao Wen-Peng, Tan Pan-Pan, Liu Jing, Zhao Jing, Zhou Bian-Hua

机构信息

Henan Provincial Open Laboratory of Key Disciplines, Environment and Animal Products Safety, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, 471000, People's Republic of China.

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan, 471003, People's Republic of China.

出版信息

Biol Trace Elem Res. 2017 Aug;178(2):253-260. doi: 10.1007/s12011-016-0929-3. Epub 2017 Jan 7.

DOI:10.1007/s12011-016-0929-3
PMID:28064417
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.

摘要

将总共84只健康雌性小鼠置于不同浓度的氟化钠(F)(饮用水中分别为0、50、100、150毫克F/L,持续90天)环境中,然后与健康雄性小鼠交配1周,以研究过量氟对雌性生殖功能的影响,特别是对胚胎着床的影响。评估雌性小鼠的怀孕率、产仔数和出生体重。通过透射电子显微镜(TEM)观察子宫组织的超微结构变化。通过定量实时PCR测定MMP-9和TIMP-1的mRNA表达水平。通过蛋白质印迹法分析MMP-9和TIMP-1的蛋白质表达水平。结果显示,暴露于氟的小鼠产仔数显著减少。与对照组相比,接受150毫克/升F处理90天的小鼠子宫组织的TEM图像显示细胞核模糊、微绒毛减少、溶酶体增加、内质网扩张和线粒体空泡化。在结构受损后,F 150组子宫组织中MMP-9和TIMP-1的表达水平显著失调。这些结果表明,MMP-9/TIMP-1系统紊乱和子宫组织结构变化与氟诱导的生殖功能障碍有关。

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