Gestational hypothyroxinemia causes an inflammatory environment at maternal-fetal tissues and fetal brain with impaired hippocampal dendritic spine maturation in the offspring

Gestational hypothyroxinemia (HTX) is associated with cognitive impairments and autism traits in offspring. However, the underlying mechanisms remain unclear. Prenatal inflammation impairs cortical development and induces diverse neurodevelopmental outcomes. Since thyroid dysfunction elicits inflammation, we sought to investigate whether HTX triggers prenatal pro-inflammatory responses. Using a mouse model of gestational HTX, we found elevated levels of IL-6 and IL-17 A in maternal serum, placental tissues, and embryonic brains at embryonic day (E)14 compared to euthyroid (EUT) dams. We also found increased proportions of dendritic cells, NK cells, M1-like macrophages, and monocytes in the placental tissues of HTX dams. Furthermore, gestational HTX exposure led to reduced Tbr2⁺ progenitors, increased Tbr1⁺ neurons, and an expanded Iba1⁺ microglial population in HTX-exposed embryos compared to EUT-exposed embryos. At postnatal day (P)55, the offspring gestated under HTX exhibited reduced hippocampal dendritic spine density and maturity compared to the progeny gestated under EUT. Notably, restoring T<sub>4</sub> levels during HTX induction (HTX + T<sub>4</sub> dams) prevented these alterations during pregnancy and in the offspring of HTX + T<sub>4</sub> dams. These findings show that gestational HTX causes inflammation during pregnancy and has neurodevelopmental effects on the progeny, opening new pathways related to how maternal HTX impairs neurodevelopment in the offspring.

Authors

Institutions

Publication Details

Journal
Scientific Reports
Published
2025-11-26
DOI
https://doi.org/10.1038/s41598-025-26206-7
Primary Topic
Thyroid Disorders and Treatments
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Gestational hypothyroxinemia causes an inflammatory environment at maternal-fetal tissues and fetal brain with impaired hippocampal dendritic spine maturation in the offspring

Elena Mery, Claudia A. Riedel, Pablo A. González, Susan M. Bueno et al.
Scientific Reports
Thyroid Disorders and Treatments
article

Gestational hypothyroxinemia causes an inflammatory environment at maternal-fetal tissues and fetal brain with impaired hippocampal dendritic spine maturation in the offspring

Elena Mery, Claudia A. Riedel, Pablo A. González, Susan M. Bueno, Ma. Andreina Rangel-Ramírez, Enrique González-Madrid, Leandro J. Carreño, Alexis M. Kalergis, Gonzalo I. Cancino, Sebastián Espinoza, Luisa F. Duarte, Felipe Simón, Daniela Elgueta, María Cecilia Opazo, Álvaro O. Ardiles, Jorge A. Soto
article en

Abstract

Gestational hypothyroxinemia (HTX) is associated with cognitive impairments and autism traits in offspring. However, the underlying mechanisms remain unclear. Prenatal inflammation impairs cortical development and induces diverse neurodevelopmental outcomes. Since thyroid dysfunction elicits inflammation, we sought to investigate whether HTX triggers prenatal pro-inflammatory responses. Using a mouse model of gestational HTX, we found elevated levels of IL-6 and IL-17 A in maternal serum, placental tissues, and embryonic brains at embryonic day (E)14 compared to euthyroid (EUT) dams. We also found increased proportions of dendritic cells, NK cells, M1-like macrophages, and monocytes in the placental tissues of HTX dams. Furthermore, gestational HTX exposure led to reduced Tbr2⁺ progenitors, increased Tbr1⁺ neurons, and an expanded Iba1⁺ microglial population in HTX-exposed embryos compared to EUT-exposed embryos. At postnatal day (P)55, the offspring gestated under HTX exhibited reduced hippocampal dendritic spine density and maturity compared to the progeny gestated under EUT. Notably, restoring T<sub>4</sub> levels during HTX induction (HTX + T<sub>4</sub> dams) prevented these alterations during pregnancy and in the offspring of HTX + T<sub>4</sub> dams. These findings show that gestational HTX causes inflammation during pregnancy and has neurodevelopmental effects on the progeny, opening new pathways related to how maternal HTX impairs neurodevelopment in the offspring.

Scientific ReportsVol. 15(1)
Universidad de Santiago de Chile (CL), Universidad del Desarrollo (CL), Pontificia Universidad Católica de Chile (CL), Clínica Alemana (CL), Universidad de las Américas (NI), University of the Americas (CL), Universidad Andrés Bello (CL), Instituto de Neurociencia Biomédica (CL), Center for Climate and Resilience Research (CL), Millennium Institute on Immunology and Immunotherapy (CL), University of Chile (CL), University of Valparaíso (CL)
Institut Català de Nanociència i Nanotecnologia, Instituto Milenio en Inmunología e Inmunoterapia, Agencia Nacional de Investigación y Desarrollo
Openalex Percentile: Top 51%
Thyroid Disorders and Treatments
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.