Aspectos morfofisiológicos e comportamentais após inflamação induzida por LPS durante a gestação de camundongos

Abstract

In mammalian, there is a lymphocyte influx in early pregnancy, which is accompanied by proliferation, differentiation and migration of these cells. These lynphocites distribute in mesometrial region of each embryo implantation site (EIS). Immunocytochemical studies indicated that these cells are Natural Killer cells, but their peculiar morphology and behavior suggest that they represent a uterus specific NK subpopulation during pregnancy called uterine Natural Killer cells (uNK). The known function for these cells in mice is cytokines releasing such as IFN- leading to decidual spiral arteries dilation and maintaining decidual integrity, contributing to normal development of decidua and placenta. Intrauterine infection was recognized as primary cause of preterm labor and supports the periventricular leukomalacia and bronchopulmonary dysplasia development. Recent study in pregnant mice showed that E.coli LPS intra-uterine injection causes increased expression of Phosphodiesterase 4B (PDE4B) and fosfodiestrase activity in maternal-fetal interface, increased TNF-α, IL-1β, IL-6 and IL-10 concentrations in amniotic fluid which leads to premature delivery and reduced fetal viability. It is expected that LPS administration promotes systemic and central proinflammatory cytokines increasing, and that the animal responds with endocrine, immune and behavioral disorders with the aim of promoting homeostasis restoration. In this context, the present study evaluated the behavioral effects of LPS administration in mice and the effects on pregnant uterus and uNK cells of these animals through morphological, cytochemical and stereological study. The feverish behavior establishment was identified from second hour after LPS administration, and this event was concomitant with anxiety-like behavior establishment. It was possible to identify treated animals apathy behavior, reduction in exploratory capacity and depressive behavior drawn 1 hour after LPS application as part of sickness behavior. The treatment also caused changes in the intrauterine environment, so that we could identify a significant increase of immature uNK cells in myometrium region of EIS. Furthermore, the treatment decreased the amount of mature and senescent uNK cells in the three EIS studied regions, concomitantly with the increasing granules and surface N-actilegalactosamine expression altered uNK cells. These changes were accompanied by the perforin labeling loss and a reduction on blood vessel α-actin labeling, suggesting respectively the uNK cell citotoxicity (perforin releasing) and actin contractile filament despolymerization causing relaxation of blood vessels that supplies the decidua and embryo.