PMID- 37941438
OWN - NLM
STAT- Publisher
LR  - 20240201
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 197
IP  - 2
DP  - 2023 Nov 6
TI  - Fetoplacental Disposition and Toxicity of Cadmium in Mice Lacking the Bcrp 
      Transporter.
PG  - 132-46
LID - kfad115 [pii]
LID - 10.1093/toxsci/kfad115 [doi]
AB  - The environmental toxicant cadmium (Cd) impairs the growth of rodents and humans 
      in utero which in turn heightens susceptibility to diseases later in life. We 
      previously demonstrated that the maternal-facing efflux transporter, breast 
      cancer resistance protein (human BCRP/ABCG2, mouse Bcrp/Abcg2) confers resistance 
      against Cd toxicity in human trophoblasts. In the current study, we sought to 
      determine whether the absence of Bcrp alters the fetoplacental disposition and 
      toxicity of Cd in mice. Pregnant female wild-type (WT) and Bcrp-null mice 
      (n = 9-10/group) were administered a single injection of saline (5 ml/kg) or 
      CdCl2 (5 mg/kg) on gestational day (GD) 9. Following Cd treatment, Bcrp-null 
      offspring were shorter and accumulated more Cd in their placentas on GD 17 
      compared to WT mice. Because Cd can adversely impact placentation and 
      transplacental nutrient delivery in mice, multiple pathways were assessed using 
      morphometrics and immunohistochemistry including placenta zonation, vasculature 
      development, and nutrient transporter expression. Most notably, the placentas of 
      Bcrp-null mice had reduced immunostaining of the cell adhesion marker, beta-catenin, 
      and the trophoblast marker, cytokeratin, as well as decreased expression of 
      divalent metal nutrient transporters (Dmt1, Zip14, and ZnT1) following Cd 
      treatment. In summary, the absence of Bcrp expression increased placental 
      concentrations of Cd which was associated with shorter fetal size that may be 
      related to differential changes in molecular patterns of placental development 
      and nutrition.
CI  - (c) The Author(s) 2023. 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 - Kozlosky, Danielle
AU  - Kozlosky D
AUID- ORCID: 0000-0002-0713-0540
AD  - Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School 
      of Pharmacy, Piscataway, NJ, 08854, USA.
FAU - Doherty, Cathleen
AU  - Doherty C
AUID- ORCID: 0000-0001-8831-6330
AD  - Environmental and Occupational Health Sciences Institute, Rutgers University, 
      Piscataway, NJ, 08854, USA.
FAU - Buckley, Brian
AU  - Buckley B
AUID- ORCID: 0000-0001-7336-4321
AD  - Environmental and Occupational Health Sciences Institute, Rutgers University, 
      Piscataway, NJ, 08854, USA.
FAU - Goedken, Michael J
AU  - Goedken MJ
AUID- ORCID: 0009-0005-8842-8371
AD  - Research Pathology Services, Rutgers University, Piscataway, NJ, 08854, USA.
FAU - Miller, Richard K
AU  - Miller RK
AUID- ORCID: 0000-0002-6691-7538
AD  - School of Medicine and Dentistry, University of Rochester Medical Center, 
      Rochester, NY, 14642, USA.
FAU - Huh, Dan Dongeun
AU  - Huh DD
AUID- ORCID: 0000-0002-5718-6884
AD  - Department of Bioengineering, School of Engineering and Applied Science, 
      University of Pennsylvania, Philadelphia, PA, 19104, USA.
FAU - Barrett, Emily S
AU  - Barrett ES
AUID- ORCID: 0000-0001-9463-524X
AD  - Environmental and Occupational Health Sciences Institute, Rutgers University, 
      Piscataway, NJ, 08854, USA.
AD  - School of Medicine and Dentistry, University of Rochester Medical Center, 
      Rochester, NY, 14642, USA.
AD  - Department of Biostatistics and Epidemiology, Rutgers School of Public Health, 
      Piscataway, NJ, 08854, USA.
FAU - Aleksunes, Lauren M
AU  - Aleksunes LM
AD  - Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School 
      of Pharmacy, Piscataway, NJ, 08854, USA.
AD  - Environmental and Occupational Health Sciences Institute, Rutgers University, 
      Piscataway, NJ, 08854, USA.
LA  - eng
GR  - P30 ES005022/ES/NIEHS NIH HHS/United States
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
GR  - T32 ES007148/ES/NIEHS NIH HHS/United States
GR  - UL1 TR003017/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20231106
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
SB  - IM
PMC - PMC10823776
OTO - NOTNLM
OT  - Abcg2
OT  - Bcrp
OT  - Breast cancer resistance protein
OT  - cadmium
OT  - divalent metal micronutrients
OT  - fetal growth
OT  - nutrition
OT  - placenta
OT  - zinc
EDAT- 2023/11/09 06:42
MHDA- 2023/11/09 06:42
PMCR- 2024/11/06
CRDT- 2023/11/09 03:56
PHST- 2024/11/06 00:00 [pmc-release]
PHST- 2023/11/09 06:42 [medline]
PHST- 2023/11/09 06:42 [pubmed]
PHST- 2023/11/09 03:56 [entrez]
AID - 7371314 [pii]
AID - kfad115 [pii]
AID - 10.1093/toxsci/kfad115 [doi]
PST - aheadofprint
SO  - Toxicol Sci. 2023 Nov 6;197(2):132-46. doi: 10.1093/toxsci/kfad115.