PMID- 35385113
OWN - NLM
STAT- MEDLINE
DCOM- 20220629
LR  - 20231221
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 188
IP  - 1
DP  - 2022 Jun 28
TI  - Gestational Exposure to Perchlorate in the Rat: Thyroid Hormones in Fetal Thyroid 
      Gland, Serum, and Brain.
PG  - 117-130
LID - 10.1093/toxsci/kfac038 [doi]
AB  - Iodine is essential for the production of thyroid hormones. Perchlorate is an 
      environmental contaminant that interferes with iodine uptake into the thyroid 
      gland to reduce thyroid hormone synthesis. As thyroid hormones are critical for 
      brain development, exposure to perchlorate during pregnancy is of concern for the 
      developing fetal brain. In this study, we (1) define profiles of thyroid hormone 
      in the maternal and fetal compartments of pregnant rats in response to inhibition 
      of the sodium-iodide symporter (NIS) by perchlorate and (2) expand inquiry 
      previously limited to serum to include fetal thyroid gland and brain. Perchlorate 
      was added to the drinking water (0, 1, 30, 300, and 1000 ppm) of pregnant rat 
      dams from gestational days (GD) 6-20. On GD20, blood, thyroid gland, and brain 
      were collected from the fetus and dam for thyroid hormone and molecular analyses. 
      Thyroid gland and serum thyroid hormones were dose-dependently reduced, with 
      steeper declines evident in the fetus than in the dam. The thyroid gland revealed 
      perturbations of thyroid hormone-action with greater sensitivity in the fetus 
      than the dam. Thyroid hormones and thyroid hormone-responsive gene expression 
      were reduced in the fetal cortex portending effects on brain development. These 
      findings are the first quantitative assessments of perchlorate-induced deficits 
      in the fetal thyroid gland and fetal brain. We provide a conceptual framework to 
      develop a quantitative NIS adverse outcome pathway for serum thyroid hormone 
      deficits and the potential to impact the fetal brain. Such a framework may also 
      serve to facilitate the translation of in vitro bioactivity to the downstream in 
      vivo consequences of NIS inhibition in the developing fetus.
CI  - Published by Oxford University Press on behalf of the Society of Toxicology 2022.
FAU - Gilbert, Mary E
AU  - Gilbert ME
AUID- ORCID: 0000-0001-8916-8851
AD  - Centre for Public Health and Environmental Assessment, US Environmental 
      Protection Agency, Office of Research and Development, Research Triangle Park, 
      North Carolina 27711, USA.
FAU - Hassan, Iman
AU  - Hassan I
AUID- ORCID: 0000-0001-6031-3891
AD  - Office of Air Quality Planning and Standards, US Environmental Protection Agency, 
      Research Triangle Park, North Carolina, USA.
FAU - Wood, Carmen
AU  - Wood C
AD  - Centre for Public Health and Environmental Assessment, US Environmental 
      Protection Agency, Office of Research and Development, Research Triangle Park, 
      North Carolina 27711, USA.
FAU - O'Shaughnessy, Katherine L
AU  - O'Shaughnessy KL
AUID- ORCID: 0000-0002-5167-8554
AD  - Centre for Public Health and Environmental Assessment, US Environmental 
      Protection Agency, Office of Research and Development, Research Triangle Park, 
      North Carolina 27711, USA.
FAU - Spring, Stephanie
AU  - Spring S
AD  - Centre for Public Health and Environmental Assessment, US Environmental 
      Protection Agency, Office of Research and Development, Research Triangle Park, 
      North Carolina 27711, USA.
AD  - Oak Ridge Institute for Student Education, Oak Ridge, Tennessee, USA.
FAU - Thomas, Susan
AU  - Thomas S
AD  - Centre for Public Health and Environmental Assessment, US Environmental 
      Protection Agency, Office of Research and Development, Research Triangle Park, 
      North Carolina 27711, USA.
AD  - Oak Ridge Institute for Student Education, Oak Ridge, Tennessee, USA.
FAU - Ford, Jermaine
AU  - Ford J
AD  - National Center for Computational Toxicology, US Environmental Protection Agency, 
      Office of Research and Development, Research Triangle Park, North Carolina, USA.
LA  - eng
GR  - EPA999999/ImEPA/Intramural EPA/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Perchlorates)
RN  - 0 (Thyroid Hormones)
RN  - 9679TC07X4 (Iodine)
SB  - IM
EIN - Toxicol Sci. 2023 Mar 20;192(1):129. PMID: 36749100
MH  - Animals
MH  - Brain
MH  - Female
MH  - Fetus
MH  - *Iodine
MH  - Perchlorates/metabolism/toxicity
MH  - Pregnancy
MH  - Rats
MH  - *Thyroid Gland
MH  - Thyroid Hormones
PMC - PMC10732305
MID - NIHMS1934636
OTO - NOTNLM
OT  - AOP
OT  - brain
OT  - development
OT  - neurotoxicity
OT  - perchlorate
OT  - thyroid hormone
COIS- The authors have no conflicts of interest to declare
EDAT- 2022/04/07 06:00
MHDA- 2022/06/30 06:00
PMCR- 2023/12/20
CRDT- 2022/04/06 12:16
PHST- 2022/04/07 06:00 [pubmed]
PHST- 2022/06/30 06:00 [medline]
PHST- 2022/04/06 12:16 [entrez]
PHST- 2023/12/20 00:00 [pmc-release]
AID - 6564242 [pii]
AID - 10.1093/toxsci/kfac038 [doi]
PST - ppublish
SO  - Toxicol Sci. 2022 Jun 28;188(1):117-130. doi: 10.1093/toxsci/kfac038.