Gestational hypothyroxinemia causes an inflammatory environment at maternal-fetal tissues and fetal brain with impaired hippocampal dendritic spine maturation in the offspring
Year: 2025
Type: article
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 4 levels during HTX induction (HTX + T 4 dams) prevented these alterations during pregnancy and in the offspring of HTX + T 4 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.
Source: Scientific Reports
Authors: Enrique González-Madrid, Ma. Andreina Rangel-Ramírez, María C. Opazo, Sebastián A. Espinoza, Daniela Elgueta, Gonzalo I. Cancino, Elena Mery, Álvaro O. Ardiles, Luisa F. Duarte, Jorge A. Soto, Leandro J. Carreño, Felipe Simon, Susan M. Bueno, Pablo A. González, Alexis M. Kalergis, Claudia A. Riedel
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: ROLE OF INOSITOL-REQUIRING ENZYME 1ALPHA (IRE-1ALPHA) ENDONUCLEASE ACTIVITY IN HERPES SIMPLEX VIRUS TYPE 1-INDUCED LIPID DROPLET ACCUMULATION AND CYCLOOXYGENASE-2 (COX-2) INDUCTION IN MURINE DENDRITIC CELLS, ROLE OF NEUROPEPTIDES IN NEURON AND BRAIN INFECTION WITH HSV-1 EVALUATION OF ANTIVIRAL ACTIVITY AND PROTECTIVE EFFECTS OVER BRAIN DAMAGE UPON INFECTION IN VIVO, DISSECTING THE CROSSTALK BETWEEN NKT CELLS AND B CELLS THAT MODULATE HUMORAL IMMUNITY BY USING A PARTIALLY HUMANIZED MOUSE MODEL, ROLE OF ENDOTHELIAL ALPHA7NACHR ACTIVITY IN COAGULATION DURING SEPSIS, PANNEXIN 1 CHANNEL: A MOLECULAR HUB FOR CONTROLLING SYNAPTIC ACTIVITY, CALCIUM SIGNALS, AND SYNAPTIC DEFECTS IN ALZHEIMER'S DISEASE., THE ANTAGONISTIC FUNCTIONS OF PTPRD AND ABL1 DURING THE DEVELOPMENT OF THE EMBRYONIC CORTEX AND ITS IMPLICATIONS IN NEURODEVELOPMENTAL DISORDERS, "IDENTIFYING THE MOLECULAR AND CELLULAR MECHANISMS LEADING TO AUTISTIC-LIKE PHENOTYPE IN THE OFFSPRING GESTATED IN HYPOTHYROXINEMIA", CHARACTERIZATION OF THE PHENOTYPIC CHANGES INDUCED BY HUMAN METAPNEUMOVIRUS INFECTION ON INNATE CELL TYPES AND THEIR EFFECT ON THE ACTIVATION OF T LYMPHOCYTES., G6481653303, MILLENNIUM INSTITUTE ON IMMUNOLOGY AND IMMUNOTHERAPY, MATERNAL MULTIPLE SCLEROSIS EFFECT ON OFFSPRING NEURAL DEVELOPMENT IN THE MURINE MODEL OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, EXPLORING THE IMMUNOMODULATORY EFFECTS OF VITAMIN D IN NEUTROPHIL RESPONSES DURING BACTERIAL INFECTIONS, EVALUATION OF THE CAPACITY OF A BCG-BASED RECOMBINANT VACCINE TO INDUCE PROTECTIVE IMMUNITY IN NEONATES AND PREVENT HRSV-MEDIATED DISEASE
OpenAlex ID: W4416717777