Browsing by Author "Rangel-Ramírez, Ma. Andreina"

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    Gestational hypothyroxinemia causes an inflammatory environment at maternal-fetal tissues and fetal brain with impaired hippocampal dendritic spine maturation in the offspring
    (2025) González-Madrid, Enrique; Rangel-Ramírez, Ma. Andreina; Opazo, María C.; Espinoza Soto, Sebastián Andrés; Elgueta Bustos, Daniela Paz; Cancino Lobos, Gonzalo Ignacio; Mery, Elena; Ardiles, Álvaro O.; Duarte, Luisa F.; Soto, Jorge A.; Carreño, Leandro J.; Simon, Felipe; Bueno Ramírez, Susan Marcela; González Muñoz, Pablo Alberto; Kalergis Parra, Alexis Mikes; Riedel, Claudia A.
    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 T4 levels during HTX induction (HTX + T4 dams) prevented these alterations during pregnancy and in the offspring of HTX + T4 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.