Maternal cadmium exposure reduces placental zinc transport and induces fetal growth restriction in mice.
Cadmium (Cd) is linked with increased risk of fetal growth restriction (FGR). Nevertheless, the mechanism remains unknown. This study established a mouse model of Cd-induced FGR through two exposure methods. Pregnant mice were either administered with CdCl2 (5, 50 and 250ppm) throughout pregnancy through drinking water or intraperitoneally injected with CdCl2 (4.5mg/kg) on GD9. As expected, fetal weight and crown-rump length were reduced in a gender-independent manner. Interestingly, Mt1 and Mt2, two metallothionein genes, were up-regulated in maternal liver. Correspondingly, Cd accumulated mainly in maternal liver and kidney, and only trace amounts of Cd could pass from dam to placentas and fetuses. Further analysis showed that placental Zn concentration was elevated. Conversely, embryonic Zn concentration was reduced. Moreover, placental Znt1 and Znt2, two zinc transporters, were down-regulated in Cd-exposed mice. These results suggest that maternal Cd exposure during pregnancy reduces placental Zn transport and induces fetal growth restriction.
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Hua
H
Wang
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Ying
Y
Wang
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Qing-Li
QL
Bo
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Yan-Li
YL
Ji
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Lu
L
Liu
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Yong-Fang
YF
Hu
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Yuan-Hua
YH
Chen
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Jun
J
Zhang
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Ling-Li
LL
Zhao
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China. Electronic address: xudex@126.com.
De-Xiang
DX
Xu
D000818:Animals; D002104:Cadmium / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D027682:Cation Transport Proteins / Q000235:genetics; D015536:Down-Regulation; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D015032:Zinc / Q000097:blood / Q000378:metabolism*
D027682:Cation Transport Proteins; D004785:Environmental Pollutants; C491054:Mt2 protein, mouse; C485803:Slc30a1 protein, mouse; C543309:Znt2 protein, mouse; C525355:metallothionein-1, mouse; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc
Cadmium; Fetal growth restriction; Mouse; Placenta; Pregnancy; Zinc