PMID- 35212737
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20230226
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 187
IP  - 2
DP  - 2022 May 26
TI  - Gestational Cd Exposure in the CD-1 Mouse Sex-Specifically Disrupts Essential 
      Metal Ion Homeostasis.
PG  - 254-266
LID - 10.1093/toxsci/kfac027 [doi]
AB  - In CD-1 mice, gestational-only exposure to cadmium (Cd) causes female-specific 
      hepatic insulin resistance, metabolic disruption, and obesity. To evaluate 
      whether sex differences in uptake and changes in essential metal concentrations 
      contribute to metabolic outcomes, placental and liver Cd and essential metal 
      concentrations were quantified in male and female offspring perinatally exposed 
      to 500 ppb CdCl2. Exposure resulted in increased maternal liver Cd+2 
      concentrations (364 microg/kg) similar to concentrations found in non-occupationally 
      exposed human liver. At gestational day (GD) 18, placental Cd and manganese 
      concentrations were significantly increased in exposed males and females, and 
      zinc was significantly decreased in females. Placental efficiency was 
      significantly decreased in GD18-exposed males. Increases in hepatic Cd 
      concentrations and a transient prenatal increase in zinc were observed in exposed 
      female liver. Fetal and adult liver iron concentrations were decreased in both 
      sexes, and decreases in hepatic zinc, iron, and manganese were observed in 
      exposed females. Analysis of GD18 placental and liver metallothionein mRNA 
      expression revealed significant Cd-induced upregulation of placental 
      metallothionein in both sexes, and a significant decrease in fetal hepatic 
      metallothionein in exposed females. In placenta, expression of metal ion 
      transporters responsible for metal ion uptake was increased in exposed females. 
      In liver of exposed adult female offspring, expression of the divalent cation 
      importer (Slc39a14/Zip14) decreased, whereas expression of the primary exporter 
      (Slc30a10/ZnT10) increased. These findings demonstrate that Cd can preferentially 
      cross the female placenta, accumulate in the liver, and cause lifelong 
      dysregulation of metal ion concentrations associated with metabolic disruption.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      Society of Toxicology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Jackson, Thomas W
AU  - Jackson TW
AUID- ORCID: 0000-0002-7996-0412
AD  - Center for Human Health and the Environment, Department of Biological Sciences, 
      North Carolina State University, 127 David Clark Labs Campus Box 7617, Raleigh, 
      North Carolina 27695, USA.
FAU - Baars, Oliver
AU  - Baars O
AD  - Department of Entomology and Plant Pathology, North Carolina State University, 
      Raleigh, North Carolina 27695, USA.
FAU - Belcher, Scott M
AU  - Belcher SM
AUID- ORCID: 0000-0002-1196-3705
AD  - Center for Human Health and the Environment, Department of Biological Sciences, 
      North Carolina State University, 127 David Clark Labs Campus Box 7617, Raleigh, 
      North Carolina 27695, USA.
LA  - eng
GR  - P30 ES025128/ES/NIEHS NIH HHS/United States
GR  - T32 ES007046/ES/NIEHS NIH HHS/United States
GR  - 5T32ES007046-38/ES/NIEHS NIH HHS/United States
GR  - P30ES025128/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Cation Transport Proteins)
RN  - 0 (SLC39A14 protein, mouse)
RN  - 00BH33GNGH (Cadmium)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 9038-94-2 (Metallothionein)
RN  - E1UOL152H7 (Iron)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Animals
MH  - Cadmium/toxicity
MH  - *Cation Transport Proteins/genetics/metabolism
MH  - Female
MH  - Homeostasis
MH  - Iron/metabolism
MH  - Liver/metabolism
MH  - Male
MH  - Manganese/metabolism/toxicity
MH  - Metallothionein/genetics/metabolism
MH  - Mice
MH  - *Placenta/metabolism
MH  - Pregnancy
MH  - Zinc/toxicity
PMC - PMC9154225
OTO - NOTNLM
OT  - epigenetic
OT  - essential metals
OT  - gestation
OT  - metallothionein
OT  - placenta
EDAT- 2022/02/26 06:00
MHDA- 2022/06/03 06:00
PMCR- 2023/02/25
CRDT- 2022/02/25 12:22
PHST- 2022/02/26 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2022/02/25 12:22 [entrez]
PHST- 2023/02/25 00:00 [pmc-release]
AID - 6536982 [pii]
AID - kfac027 [pii]
AID - 10.1093/toxsci/kfac027 [doi]
PST - ppublish
SO  - Toxicol Sci. 2022 May 26;187(2):254-266. doi: 10.1093/toxsci/kfac027.