PMID- 38133428
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231225
IS  - 2305-6304 (Electronic)
IS  - 2305-6304 (Linking)
VI  - 11
IP  - 12
DP  - 2023 Dec 18
TI  - Structural Malformations in the Neonatal Rat Brain Accompany Developmental 
      Exposure to Ammonium Perchlorate.
LID - 10.3390/toxics11121027 [doi]
LID - 1027
AB  - Environmental contaminants are often flagged as thyroid system disruptors due to 
      their actions to reduce serum thyroxine (T4) in rodent models. The presence of a 
      periventricular heterotopia (PVH), a brain malformation resulting from T4 
      insufficiency, has been described in response to T4 decrements induced by 
      pharmaceuticals that reduce the hormone synthesis enzyme thyroperoxidase. In this 
      report, we extend these observations to the environmental contaminant 
      perchlorate, an agent that interferes with thyroid status by inhibiting iodine 
      uptake into the thyroid gland. Pregnant rat dams were administered perchlorate in 
      their drinking water (0, 30, 100, 300, 1000 ppm) from gestational day (GD) 6 
      until the weaning of pups on postnatal day (PN) 21. Serum T4 was reduced in dams 
      and fetuses in late gestation and remained lower in lactating dams. Pup serum and 
      brain T4, however, were not reduced beyond PN0, and small PVHs were evident in 
      the brains of offspring when assessed on PN14. To emulate the developmental time 
      window of the brain in humans, a second study was conducted in which pups from 
      perchlorate-exposed dams were administered perchlorate orally from PN0 to PN6. 
      This treatment reduced serum and brain T4 in the pup and resulted in large PVH. A 
      third study extended the period of serum and brain TH suppression in pups by 
      coupling maternal perchlorate exposure with maternal dietary iodine deficiency 
      (ID). No PVHs were evident in the pups from ID dams, small PVHs were observed in 
      the offspring of dams exposed to 300 ppm of perchlorate, and very large PVHs were 
      present in the brains of pups born to dams receiving ID and perchlorate. These 
      findings underscore the importance of the inclusion of serum hormone profiles in 
      pregnant dams and fetuses in in vivo screens for thyroid-system-disrupting 
      chemicals and indicate that chemical-induced decreases in fetal rat serum that 
      resolve in the immediate postnatal period may still harbor considerable concern 
      for neurodevelopment in humans.
FAU - Gilbert, Mary E
AU  - Gilbert ME
AUID- ORCID: 0000-0001-8916-8851
AD  - Centre for Public Health and Environmental Assessment, Office of Research and 
      Development, Environmetal Protection Agency, Research Triangle Park, NC 27709, 
      USA.
FAU - O'Shaughnessy, Katherine L
AU  - O'Shaughnessy KL
AD  - Centre for Public Health and Environmental Assessment, Office of Research and 
      Development, Environmetal Protection Agency, Research Triangle Park, NC 27709, 
      USA.
FAU - Bell, Kiersten S
AU  - Bell KS
AD  - College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
FAU - Ford, Jermaine L
AU  - Ford JL
AD  - National Center for Computational Toxicology, Office of Research and Development, 
      Environmental Protection Agency, Research Triangle Park, NC 27709, USA.
LA  - eng
PT  - Journal Article
DEP - 20231218
PL  - Switzerland
TA  - Toxics
JT  - Toxics
JID - 101639637
PMC - PMC10747616
OTO - NOTNLM
OT  - AOP
OT  - brain
OT  - development
OT  - neurotoxicity
OT  - perchlorate
OT  - thyroid hormone
COIS- The authors declare no conflict of interest.
EDAT- 2023/12/22 12:41
MHDA- 2023/12/22 12:42
PMCR- 2023/12/18
CRDT- 2023/12/22 09:27
PHST- 2023/11/06 00:00 [received]
PHST- 2023/12/11 00:00 [revised]
PHST- 2023/12/11 00:00 [accepted]
PHST- 2023/12/22 12:42 [medline]
PHST- 2023/12/22 12:41 [pubmed]
PHST- 2023/12/22 09:27 [entrez]
PHST- 2023/12/18 00:00 [pmc-release]
AID - toxics11121027 [pii]
AID - toxics-11-01027 [pii]
AID - 10.3390/toxics11121027 [doi]
PST - epublish
SO  - Toxics. 2023 Dec 18;11(12):1027. doi: 10.3390/toxics11121027.