Science Inventory

Structural Abnormalities and Learning Impairments Induced by Low Level Thyroid Hormone Insufficiency: A Cross-Fostering Study

Citation:

Gilbert, M., W. Oshiro, S. Spring, M. Hotchkiss, Pat Kosian, AND S. Degitz. Structural Abnormalities and Learning Impairments Induced by Low Level Thyroid Hormone Insufficiency: A Cross-Fostering Study. Presented at Intl. Neurotoxicology Association Meeting, Montreal, Qu, CANADA, June 27 - July 01, 2015.

Impact/Purpose:

Will be presented at the International Neurotoxicology Association Meeting, Montreal, Quebec, Canada, June 27-July1, 2015

Description:

Severe reductions in thyroid hormones (TH) during development alter brain structure and impair learning. Uncertainty surrounds both the impact oflower levels of TH disruption and the sensitivity of available metrics to detect neurodevelopmental deficits of this disruption. We have demonstrated dose-dependent impairments in fear conditioning (FC) in offspring of rat dams exposed to graded levels of the goitrogen propylthiouracil (PTU) throughout gestation and lactation. Similarly, we have observed a structural anomaly in the brain, a subcortical band heterotopia (SBH), of exposed offspring. The present study was designed to determine the window of exposure critical for the induction of these two phenotypic outcomes. Pregnant rats (n=32) were administered PTU via drinking water (0 or 3ppm) from gestational day (GD) 6 to postnatal day (PN) 14. On PN2, half the offspring from each control litter was crossfostered to a PTU nursing dam, and reciprocally half of each PTU litter was crossfostered to control dams, creating 4 treatment groups: pups receiving PTU primarily prenatally (PTU-CON); postnatally (CON-PTU), not at all (CON-CON), or throughout the pre- and postnatal period (PTU-PTU).Blood was sampled from dams via tail bleeds during pregnancy (GD 10,15,20) and lactation (PNS,10,14,18), and trunk blood was collected on PN21 at weaning of the pups. Pups were sacrificed and blood and brains collected on days corresponding to dam tail bleeds. Brains were fixed and prepared for immunohistochemistry for detection of SBH. One male and one female pup from each litter/treatment were tested as adults (PN55-65) on FC. We observed the presence of SBH in brains of male and female neonates on PN14 and PN18 exposed prenatally (PTU­ CON and PTU-PTU) but not with exposure limited to the postnatal period (CON-PTU).Significant deficits were seen in FC in male but not female offspring, and were limited to animals exposed throughout gestation and lactation (PTU-PTU). These findings indicate that distinct phenotypes are produced when TH insufficiency occurs over different periods of brain development. These results agree with previous findings of a greater susceptibility to behavioral impairments in male offspring, and suggest that behavioral deficits appear independent of the formation of a SBH. Does not reflect EPA policy

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 07/01/2015
Record Last Revised: 11/18/2016
OMB Category: Other
Record ID: 309481

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

TOXICOLOGY ASSESSMENT DIVISION

ENDOCRINE TOXICOLOGY BRANCH