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 / Effect of maternal hypothyroidism on the spatiotemporal expression of immunological mediators and population of Natural Killers cells in decidua and metrial gland of rats

Estudou-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+.(AU)

The 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.(AU)

Thyroid hormones affect decidualization and angiogenesis in the decidua and metrial gland of rats / Hormônios tireoidianos afetam a decidualização e a angiogênese na decídua e glândula metrial de ratas

This study aimed to evaluate the effects of thyroid hormone on the decidua and metrial gland of rats and to examine the expression of angiogenic factors. 72 adult, female rats were divided into hypothyroid, T4-treated2, and control groups. At 10, 14 and 19 days of gestation (DG), the decidua and metrial gland were collected for histomorphometric and immunohistochemical evaluation of the expression of VEGF, Flk-1 and Tie-2. Hypothyroidism reduced the area of the decidua at 10 and 19 DG. Furthermore, VEGF was increased at 10 and 14 DG, and Flk-1 only at 14 DG, but both was reduced at 19 DG in the metrial gland without significantly changing the area occupied by blood vessels. Rats treated with T4 showed an increase in the decidua blood vessels at 10 and 19 DG. However, at 10 DG, excess T4 resulted in increased of Flk-1 in the decidua and metrial gland. Hypothyroidism increased the Tie-2 at 10 and 19 DG in the decidua and metrial gland. In conclusion, hypothyroidism reduces the area of the decidua and increases the expression of VEGF, Tie-2 and Flk-1. The excess of T4 promotes tissue angiogenesis by increasing the number of vessels in the decidua because of the increased expression of Flk-1.(AU)

Este estudo teve como objetivo avaliar os efeitos dos hormônios tireoidianos sobre a decídua e a glândula metrial pela análise da expressão de fatores angiogênicos em ratas. 72 ratas adultas, fêmeas foram distribuídas nos grupos hipotiroideo, tratado com T4 e controle. Aos 10, 14 e 19 dias de gestação (DG), a decídua e a glândula metrial foram coletadas para avaliação histomorfométrica e imunoistoquímica da expressão de VEGF, Flk-1 e Tie-2. O hipotireoidismo reduziu a área da decídua aos 10 e 19 DG. Além disso, o VEGF aumentou aos 10 e 14 DG e o Flk-1 apenas aos 14 DG, mas ambos foram reduzidos aos 19 DG na glândula metrial sem alterar significativamente a área ocupada pelos vasos sanguíneos. As ratas tratadas com T4 apresentaram aumento do número de vasos sanguíneos na decídua aos 10 e 19 DG. Além disso, aos 10 DG, o excesso de T4 resultou no aumento de Flk-1 na decídua e na glândula metrial. O hipotireoidismo aumentou o Tie-2 em 10 e 19 DG na decídua e na glândula metrial. Desta forma, pode-se concluir que o hipotireoidismo reduz a área da decídua e aumenta a expressão de VEGF, Tie-2 e Flk-1. O excesso de T4 promove a angiogênese tecidual ao aumentar o número de vasos na decídua devido ao aumento da expressão de Flk-1.(AU)

Development of uteroplacental vasuclature, granulated metrial gland cells and trophoblasts in the uterine wall of the mouse during pregnancy

The development of the uteroplacental vasculature was studied by Indian ink injection method. The non-pregnant [estrus] endometrium was supplied by radial and terminal arteries. On day 5 of pregnancy the radial arteries became spiral arteries. All these changes appeared as an indication for the increased uterine blood volume. In this early five days interval of rapid development prior to blastocyst attachment, the endometrium underwent a decidual reaction by transforming its fusiform stromal cells into large polyhedral cells [decidual cells]. Ultrastructurally, their processes appeared to penetrate the basement membranes of the uterine epithelial cells and might aid in its disintegration. In the subsequent stages [days 6-8 of pregnancy] during the initial stages of invasion of the endometrial stroma by the embryo, most trophoblastic cells surrounding the blastocyst were flat [or roughly low cuboidal]. As pregnancy proceeded [on day 8], the area occupied by the trophoblasts became larger and some of these cells became giant. This was associated with an activation of the giant cells and their aquistion of invasive behavior, to complete the process of implantation previously experienced by decidual cells. From day 8 to day 14, the products of conception continued to enlarge at the expence of th surrounding endometrium. On day 8 erosion of endometrial blood vessels became more extensive. The outward growth of the trophoblasts from the trophoblastic shell forming primary villi. When the latter villi were invaded by mesenchymal connective tissue and branches of the umbilical arteries, they were termed chorionic villi. This was the anatomical bases for the achievement of the labyrinthine hemochorial placenta which increases in size in the subsequent stages [11-14 days]. It was considered the first step towards establishing the uteroplacental circulation on which the growth of the embryo will later depend. Numerous GMG cells characterized by their PAS positive cytoplasmic granules were found to differentiate in the deciduas basalis and metrial glands of the uterine wall during the first half of pregnancy [till day 8]. By day 8 and the subsequent stages of pregnancy some of the GMG cells were lying adjacent to the labyrinthine placenta

Patología de la placenta de rata inducida por la deficiencia de ácidos grasos / Pathology of placenta of rats induced by fatty acid deficiency

Los lípidos son componentes importantes de las células, tanto desde el punto de vista estructural como funcional. Además de intervenir en funciones de transporte, reconocimiento celular e inmunidad, los Acidos Grasos Esenciales (AGE) , son importantes para el mantenimiento funcional y estructural de los organismos animales. En nuestro laboratorio se demostró que ratas preñadas alimentadas con dietas deficientes en ácidos grasos esenciales (DAGE ) y otras con las mismas dietas pero suplementadas con 5 por ciento de aceite de maíz, ( rico en ácido linoleico ) mostraron alteraciones en el desarrollo placentario. En el presente trabajo, 57 ratas hembras de una cepa Wistar fueron alimentadas desde el destete con una de las siguientes dietas: 1: DAGE; 2 :DAM (dieta DAGE más aceite de maíz , alta proporción de ácido linoléico); 3: DAS (dieta DAGE más aceite de soja, alta proporción de ácidos linoleico y a-linolénico) y 4 :DC (dieta comercial). Después de los 3 meses de edad los animales fueron preñados y se sacrificaron al 13 día de la gestación. Los cuernos uterinos fueron disecados y los sitios de implantación se fijaron en formol y se incluyeron en parafina. Las observaciones se realizaron sobre cortes coloreados con H/E , y se estudió la placenta corioalantoidea , el número de implantaciones y el de reabsorciones . La glándula metrial de ratas DAGE y DAM presentaron modificaciones estructurales en relación a las DC. Los hallazgos más notables fueron : Indiferenciación de las células granulares metriales y aumento de la cantidad de tejido conectivo. En las ratas DAS ,en cambio,el aspecto de la glándula metrial era similar a lo observado en el grupo DC. En los grupos DAGE y DAM el laberinto estaba ensanchado, con septos vasculares pero en el grupo DAS eran similares al DC, delgados y vasculares. No se detectaron diferencias en el número de implantaciones y reabsorciones. Los presentes resultados sugieren que el ácido a-linolénico dietético es esencial para que la placenta de rata alcance su desarrollo normal.

migration of granulated metrial cells of pregnant mouse uterus

The morphological appearance of granulated metrial gland cells of pregnant mouse uterus in the region of metrial gland, deciduas basalis, Labyrinthine placenta and lung tissue at days 11, 14, and 17 of pregnancy was examined by light microscope. Evidence of the migration of these cells to the labyrinthine placenta suggested that this may be of importance in the functional activity of these cells to the labyrinthine placenta