Efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e população de células natural killers na decídua e na glândula metrial de ratas

Abstract

RESUMOEstudou-se o efeito do hipotireoidismo materno na expressão espaço-temporal de mediadores imunológicos e na população de células natural killers (NK) na decídua e na glândula metrial de ratas durante a gestação. Avaliou-se a detecção imunoistoquímica de interferon γ (IFNγ), do fator inibidor de migração (MIF), da interleucina 15 (IL15), do óxido nítrico sintase induzível (iNOS), a marcação com lectina DBA para evidenciação das células NK uterinas DBA + e a expressão gênica de Ifnγ e Nos2. O hipotireoidismo aumentou o iNOS aos sete dias, a IL15 e o MIF aos 10 e 12 dias, o IFNγ e o MIF aos 14 DG e a expressão dos transcritos gênicos para iNos aos 12 e 19 dias e para Ifnγ aos 14 DG. O hipotireoidismo reduziu a imunomarcação de MIF e lectina DBA aos sete dias, lectina DBA aos 10 e 14 DG, IFNγ aos 12 dias, e a expressão de Ifnγ aos 10 e 19 DG e de iNOS aos 12, 14 e 19 DG, bem como reduziu seus transcritos gênicos aos 10 e 14 DG. Conclui-se que o hipotireoidismo compromete o perfil imunológico na interface materno-fetal ao longo da gestação, particularmente por reduzir o fator anti-inflamatório iNOS e a população de células uNK DBA + . Palavras-chave: hipotireoidismo, decídua, glândula metrial, imunologia ABSTRACTThe goal of this study was to evaluate the effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats. Interferon gamma (IFNγ), migration inhibitory factor (MIF), interleukin 15 (IL15), inducible nitric oxide synthase (iNOS), and DBA-Lectin labeling for evidence of uNK DBA + cells in decidua and genetic expression of Ifnγ and iNos by real-time RT-PCR were evaluated. Hypothyroidism increased protein expression of iNOS at 7 days, IL15 and MIF at 10 and 12 days, IFNγ and MIF at 14 DG in the decidua and/or metrial gland and the gene transcripts for iNOS at 12 and 19 days and for Inf at 14 DG. In addition, hypothyroidism reduced the protein expression of MIF and DBA-Lectin at 7 days, DBA-Lectin at 10 and 14 DG, IFNγ at 12 days, and the gene transcript to Ifnγ at 10 and 19 DGs. Hypothyroidism also reduced the protein expression of iNOS at 12, 14 and 19 DG and reduced its gene transcripts at 10 and 14 DGs. It is concluded that hypothyroidism compromises the immunology profile at the maternal-fetal interface throughout pregnancy, particularly by reducing the anti-inflammatory factor iNOS and population of uNK DBA + cells.

Kisspeptin treatment improves fetal-placental development and blocks placental oxidative damage caused by maternal hypothyroidism in an experimental rat model

“…Moreover, plasma levels of triiodothyronine (T3) and thyroxine (T4) are low in patients with preeclampsia (32,33). Studies in rats have also shown that hypothyroidism reduces intrauterine trophoblast migration and proliferation, increases placental apoptosis, compromises placental morphogenesis and vascularization, causes oxidative and reticular stress, and alters the immune profile and uNK cell population at the maternal-fetal interface (34)(35)(36)(37)(38)(39)(40). However, the role of kisspeptin in these placental changes is still unknown.…”

Kisspeptin Suppresses Inflammasome-NLRP3 Activation and Pyroptosis Caused by Hypothyroidism at the Maternal-Fetal Interface of Rats

“…Maternal hypothyroidism is one of the most common gestational metabolic disorders and affects around 2–3% of the population [ 1 ]. Women with maternal hypothyroidism have an increased risk of miscarriage, premature birth, placental abruption, preeclampsia, gestational diabetes, and intrauterine growth restriction [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ], while in hypothyroid female rats the placental development is compromised, with alteration of immunology and trophoblastic endocrine function [ 7 , 9 , 10 , 11 , 12 , 13 , 14 ]. In addition, a recent study demonstrated that maternal hypothyroidism also causes oxidative stress and endoplasmic reticulum stress at the maternal-fetal interface of rats [ 15 ], suggesting that this cellular stress may result from the failure of intrauterine trophoblastic migration observed in these animals [ 12 ].…”