Maternal hypothyroidism causes oxidative stress and endoplasmic reticulum stress in the maternal-fetal interface of rats.

Autor: Dos Anjos Cordeiro JM; Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus SoaneNazare de Andrade, 45662-900, Ilheus, Brazil., Santos LC; Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus SoaneNazare de Andrade, 45662-900, Ilheus, Brazil., de Oliveira LS; Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus SoaneNazare de Andrade, 45662-900, Ilheus, Brazil., Santos BR; Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus SoaneNazare de Andrade, 45662-900, Ilheus, Brazil., Santos EO; Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus SoaneNazare de Andrade, 45662-900, Ilheus, Brazil., Barbosa EM; Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus SoaneNazare de Andrade, 45662-900, Ilheus, Brazil., de Macêdo IO; Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus SoaneNazare de Andrade, 45662-900, Ilheus, Brazil., de Freitas GJC; Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Santos DA; Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., de Lavor MSL; Hospital Veterinario, Departamento de Ciencias Agrarias e Ambientais, Universidade Estadual de Santa Cruz, Campus Soane Nazare de Andrade, 45662-900, Ilheus, Brazil., Silva JF; Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Campus SoaneNazare de Andrade, 45662-900, Ilheus, Brazil. Electronic address: jfsilva@uesc.br.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2022 Oct; Vol. 191, pp. 24-39. Date of Electronic Publication: 2022 Aug 26.
DOI: 10.1016/j.freeradbiomed.2022.08.033
Abstrakt: Maternal hypothyroidism is associated with pre-eclampsia and intrauterine growth restriction, gestational diseases involving oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the placenta. However, it is not known whether hypothyroidism also causes OS and ERS at the maternal-fetal interface. The aim was to evaluate the fetal-placental development and the expression of mediators of OS and of the unfolded protein response (UPR) in the maternal-fetal interface of hypothyroid rats. Hypothyroidism was induced in Wistar rats with propylthiouracil and the fetal-placental development and placental and decidual expression of antioxidant, hypoxia, and UPR mediators were analyzed at 14 and 18 days of gestation (DG), as well the expression of 8-OHdG and MDA, and reactive oxygen species (ROS) and peroxynitrite levels. Hypothyroidism reduced fetal weight at 14 and 18 DG, in addition to increasing the percentage of fetal death and reducing the weight of the uteroplacental unit at 18 DG. At 14 DG, there was greater decidual and/or placental immunostaining of Hif1α, 8-OHdG, MDA, SOD1, GPx1/2, Grp78 and CHOP in hypothyroid rats, while there was a reduction in placental and/or decidual gene expression of Sod1, Gpx1, Atf6, Perk, Ho1, Xbp1, Grp78 and Chop in the same gestational period. At 18 DG, hypothyroidism increased the placental ROS levels and the decidual and/or placental immunostaining of HIF1α, 8-OHdG, MDA, ATF4, GRP78 and CHOP, while it reduced the immunostaining and enzymatic activity of SOD1, CAT, GST. Hypothyroidism increased the placental mRNA expression of Hifα, Nrf2, Sod2, Gpx1, Cat, Perk, Atf6 and Chop at 18 DG, while decreasing the decidual expression of Sod2, Cat and Atf6. These findings demonstrated that fetal-placental restriction in female rats with hypothyroidism is associated with hypoxia and dysregulation in placental and decidual expression of UPR mediators and antioxidant enzymes, and activation of oxidative stress and endoplasmic reticulum stress at the maternal-fetal interface.
Competing Interests: Declaration of competing interest The author shave declared that no conflict interest exists.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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