title: Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport.
abstract: Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl2 (2.5 or 5.0mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl2. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters.
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China.
authors.forename: Gui-Bin
authors.initials: GB
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China. Electronic address: wanghuadev@126.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China.
authors.forename: Min-Yin
authors.initials: MY
authors.lastname: Guo
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, PR China. Electronic address: xudex@126.com.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D005492:Folic Acid / Q000097:blood / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D008813:Mice, Inbred ICR; D009436:Neural Tube Defects / Q000139:chemically induced*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D010929:Placentation / Q000187:drug effects; D011247:Pregnancy; D058979:Proton-Coupled Folate Transporter / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D058979:Proton-Coupled Folate Transporter; D012333:RNA, Messenger; D002104:Cadmium; D005492:Folic Acid
keywords: Cadmium; Fetal growth restriction; Folate; Neural tube defects; Placenta; Proton-coupled folate transporter