妊娠期镉胁迫致小鼠胎儿宫内生长受限小鼠胎盘的DNA甲基化研究
发布时间：2018-11-14 14:29
【摘要】：重金属镉是导致小鼠胎儿畸形以及胎儿宫内生长受限的环境污染物之一,但是镉胁迫致小鼠胎儿宫内生长受限的分子机制尚不明确。具体而言,妊娠期胎盘中营养物质转运,其中包括葡萄糖运输在镉胁迫致胎儿宫内生长受限中的作用不明确。在本学位论文研究中,我们采取方法实时定量PCR、West Blot和亚硫酸氢盐PCR等方法,通过建立镉胁迫致小鼠胎儿宫内生长受限的动物模型,探究镉对胎盘中葡萄糖转运载体GLUTs(glucose transporter)的毒性作用。结果显示,与正常对照组相比,镉处理组小鼠胎盘中GLUT3蛋白含量明显下降。通过亚硫酸氢盐PCR对小鼠胎盘DNA甲基化水平检测发现,GLUT3基因启动子区序列过度甲基化。但是,在小鼠胎盘中两个主要的重复序列LINE-1(long interspersed nucleotide element)和IAP(Intracisternal A particles)基因的甲基化水平没有明显变化。此外,在小鼠胎盘中甲基化转移酶(DNA methyltransferase)DNMT3B和DNMT3L的含量随着镉处理浓度的增加呈上升趋势。然而,甲基化转移酶DNMT1与DNMT3A的表达量没有明显变化。实验结果说明:(1)在妊娠末期,镉胁迫显著引起小鼠胎儿与胎盘重量的下降。(2)通过小鼠胎盘和胎儿组织的镉含量测定发现,镉在胎盘中积累而不是在胎儿中积累;镉胁迫引起的胎儿宫内生长受限是间接作用于胎儿,而不是胎盘。(3)镉胁迫引起的小鼠胎儿宫内生长受限,与胎盘中葡萄糖转移载体GLUT3的表达量下调有关,GLUT3表达量下降可能是由于甲基化转移酶DNMT3B和DNMT3L的过表达引起GLUT3基因启动子区序列低甲基化而引起的。
[Abstract]:Cadmium is one of the environmental pollutants leading to fetal malformation and fetal growth restriction in mice, but the molecular mechanism of fetal growth restriction induced by cadmium stress is not clear. Specifically, the transport of nutrients, including glucose, in the placenta during pregnancy is unclear in the role of cadmium stress induced fetal growth restriction. In this dissertation, we used methods such as real-time quantitative PCR,West Blot and hydrogen sulfite PCR to establish an animal model of fetal intrauterine growth restriction induced by cadmium stress in mice. To investigate the toxicity of cadmium to glucose transport vector GLUTs (glucose transporter) in placenta. The results showed that the content of GLUT3 protein in the placenta of cadmium treated mice was significantly lower than that of normal control group. By detecting the DNA methylation level of mouse placenta by PCR, we found that the promoter sequence of GLUT3 gene was hypermethylated. However, there was no significant change in methylation level of LINE-1 (long interspersed nucleotide element) and IAP (Intracisternal A particles) genes in mouse placenta. In addition, the contents of methyltransferase (DNA methyltransferase) DNMT3B and DNMT3L in mouse placenta increased with the increase of cadmium concentration. However, there was no significant change in the expression of methyltransferase DNMT1 and DNMT3A. The results showed that: (1) cadmium stress significantly decreased the weight of mouse fetus and placenta at the end of pregnancy. (2) cadmium accumulated in placenta, not in fetus. The fetal intrauterine growth restriction induced by cadmium stress is indirectly acting on the fetus, not the placenta. (3) the fetal intrauterine growth restriction induced by cadmium stress is related to the down-regulation of the expression of glucose transfer vector GLUT3 in the placenta. The decrease of GLUT3 expression may be due to the hypomethylation of the promoter region of GLUT3 gene caused by the overexpression of methyltransferase DNMT3B and DNMT3L.
【学位授予单位】：山西大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R114
[Abstract]:Cadmium is one of the environmental pollutants leading to fetal malformation and fetal growth restriction in mice, but the molecular mechanism of fetal growth restriction induced by cadmium stress is not clear. Specifically, the transport of nutrients, including glucose, in the placenta during pregnancy is unclear in the role of cadmium stress induced fetal growth restriction. In this dissertation, we used methods such as real-time quantitative PCR,West Blot and hydrogen sulfite PCR to establish an animal model of fetal intrauterine growth restriction induced by cadmium stress in mice. To investigate the toxicity of cadmium to glucose transport vector GLUTs (glucose transporter) in placenta. The results showed that the content of GLUT3 protein in the placenta of cadmium treated mice was significantly lower than that of normal control group. By detecting the DNA methylation level of mouse placenta by PCR, we found that the promoter sequence of GLUT3 gene was hypermethylated. However, there was no significant change in methylation level of LINE-1 (long interspersed nucleotide element) and IAP (Intracisternal A particles) genes in mouse placenta. In addition, the contents of methyltransferase (DNA methyltransferase) DNMT3B and DNMT3L in mouse placenta increased with the increase of cadmium concentration. However, there was no significant change in the expression of methyltransferase DNMT1 and DNMT3A. The results showed that: (1) cadmium stress significantly decreased the weight of mouse fetus and placenta at the end of pregnancy. (2) cadmium accumulated in placenta, not in fetus. The fetal intrauterine growth restriction induced by cadmium stress is indirectly acting on the fetus, not the placenta. (3) the fetal intrauterine growth restriction induced by cadmium stress is related to the down-regulation of the expression of glucose transfer vector GLUT3 in the placenta. The decrease of GLUT3 expression may be due to the hypomethylation of the promoter region of GLUT3 gene caused by the overexpression of methyltransferase DNMT3B and DNMT3L.
【学位授予单位】：山西大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R114
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相关期刊论文 前9条
1 刘莉莉;邓莹玉;周珊宇;董明;崔凡;曾玉梨;陈晓燕;赵娜;李宏玲;;低剂量镉暴露胎盘屏障作用及相关蛋白探讨[J];毒理学杂志;2015年04期
2 周京花;马慧慧;赵美蓉;刘t，
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