title: Epigenetic regulation of placental glucose transporters mediates maternal cadmium-induced fetal growth restriction.
abstract: Cadmium (Cd) is one of the most toxic environmental pollutants that cause fetal malformation and growth restriction. However, the molecular mechanisms underlying maternal Cd toxicity on fetal growth remain largely unknown. Specifically, the role of placental nutrient transporters, including glucose transporters (GLUTs), has been poorly characterized in the etiology of Cd-induced fetal growth restriction (FGR). In the present study, we established a murine model of FGR induced by maternal Cd exposure, and examined the toxic effects of Cd on placental GLUTs. Our results showed that GLUT3 is significantly downregulated in Cd-exposed mouse placentas when compared to the normal ones. Data from bisulfite PCR demonstrated the hypermethylation of the promoter region of GLUT3. However, methylation levels remained unchanged in two major repetitive elements (LINE-1 and IAP) in Cd-exposed placentas. Moreover, DNA methyltransferase (DNMT) 3B and DNMT3L were significantly upregulated in Cd-exposed placentas, and there were no expression changes of DNMT1 and DNMT3A. Collectively, our results suggest that changes in DNMT3B and DNMT3L expressions and site-specific DNA methylation may be involved in the etiology of Cd-induced fetal growth restriction through downregulation of GLUT3.
authors.affiliation: School of Life Science, Shanxi University, Taiyuan, China. Electronic address: xupeng0313@aliyun.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: School of Life Science, Shanxi University, Taiyuan, China. Electronic address: 615919286@qq.com.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Wu
authors.affiliation: School of Life Science, Shanxi University, Taiyuan, China. Electronic address: lrq20051224@aliyun.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xi
authors.affiliation: School of Life Science, Shanxi University, Taiyuan, China. Electronic address: lanwang@sxu.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D060766:Drinking Water; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000235:genetics*; D051246:Glucose Transport Proteins, Facilitative / Q000187:drug effects* / Q000235:genetics*; D051274:Glucose Transporter Type 3 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D014018:Tissue Distribution
chemical_list: C000715535:Dnmt3a protein, mouse; D060766:Drinking Water; D051246:Glucose Transport Proteins, Facilitative; D051274:Glucose Transporter Type 3; C495689:Slc2a3 protein, mouse; D002104:Cadmium; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C000619381:Dnmt1 protein, mouse
keywords: Cadmium; DNA methylation; Fetal growth restriction; Glucose transporter; Placenta