Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes.
Low thyroid hormone during pregnancy can spark autism-like traits in offspring, but early thyroid pills prevent it.
01Research in Context
What this study did
Scientists lowered thyroid hormone in pregnant mice. They watched the pups for autism-like traits.
The team tested social play, repetitive grooming, and brain inflammation. Half the moms got thyroid pills to see if it fixed the pups.
What they found
Pups from low-thyroid moms acted autistic. They played less, groomed more, and had swollen brains.
Thyroid pills during pregnancy blocked every problem. The pups grew up normal.
How this fits with other research
Tioleco et al. (2021) pooled 36 human studies. Moms who had infections while pregnant had a small rise in autism odds. Both papers point to the womb as a key window.
Hwang et al. (2013) saw more autism in babies born early. That looks opposite, but their babies were pre-term while the mice went full-term. Different start, same concern: keep the prenatal environment healthy.
Zhao et al. (2024) found moms who skipped folic acid nearly tripled autism odds. Like thyroid pills in the mouse study, folic acid is a cheap shield you can give before birth.
Why it matters
You can’t give a mouse thyroid pill to a human, but you can ask OB teams to check TSH at the first visit. If a mom’s level is low, replacement starts for pennies a day. That quick lab draw may shave a few autism cases off your future caseload.
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02At a glance
03Original abstract
<h4>Background</h4>The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring.<h4>Methods</h4>To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T<sub>4</sub>, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus.<h4>Results</h4>The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1β, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T<sub>4</sub> during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T<sub>4</sub> levels and specific ASD-like outcomes.<h4>Discussion</h4>This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.
, 2024 · doi:10.3389/fendo.2024.1381180