RESUMO
Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum-treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth.
Assuntos
Células Matadoras Naturais/citologia , Circulação Placentária/fisiologia , Pré-Eclâmpsia/fisiopatologia , Prenhez , Trofoblastos/citologia , Análise de Variância , Angiotensinogênio/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Feminino , Desenvolvimento Fetal/imunologia , Desenvolvimento Fetal/fisiologia , Idade Gestacional , Interleucina-15/metabolismo , Células Matadoras Naturais/imunologia , Circulação Placentária/imunologia , Pré-Eclâmpsia/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Estatísticas não Paramétricas , Trofoblastos/metabolismoRESUMO
El estudio histológico del tejido decidual en la rata pseudopreñada, reveló una onda constante de figuras mitóticas que, partiendo de la decidua antimesometrial, se desplazó hacia la decidua mesometrial y, finalmente, hacia el triángulo mesometrial. Este y otros cambios morfológicos, como el estudio cualitativo de la superficie endometrial con microscopia eletrónica, fueron comparados con aquellos encontrados en la rata pseudopreñada diabética. No se encontraron diferencias estadísticamente significativas en cuanto a peso uterino, distribución de figuras mitóticas, ni distribución de glicógeno en los días 7 y 10 de pseudopreñez. Tampoco se observaron diferencias cualitativas entre la superficie epitelial del grupo control y diabético. El día 13, sin embargo, se encontraron tres diferencias estadísticamente significativas. Se observó en el grupo diabético: 1) caída en el peso uterino; 2) menor incidencia de figuras mitóticas en el triángulo mesometrial, y 3) menor grado de diferenciación de las arterias espirales