Avaliação dos efeitos da Metirapona sobre a gestação de camundongos submetidos à restrição alimentar

Abstract

Gestation has neuroendocrine and physiological changes in the maternal organism, being a critical period to stressful stimuli. The animal model is widely used for the study of alterations during pregnancy, In the women uterine microenvironment, 70% of leukocytes are lymphocytes belonging to the uterine natural killer (uNK) lineage. Such cells play a role in the maintenance of pregnancy homeostasis and its absence is directly related to abortion. Nutritional changes during pregnancy can cause damages for both mother and offspring and are the subject of several studies. The aim of the present study was to analyze the effect of mettirapone, an inhibitor of glucocorticoid synthesis, and dietary restriction on gestation of Swiss mice from 1 to 10º ddg. Four groups were used: animals fed ad libitum with control ration (RC), animals fed control ration ad libitum and submitted to treatment by metyrapone (Met), animals submitted to food restriction (RA) and animals submitted to food restriction and treated with metirapone (RA + Met). Behavioral, gestational viability, morphological and cytochemical analyzes were performed through the Dolichos biflorus agglutinin lectin, which reacts specifically with the plasma membrane and uNK granules. Such uNK cells reactive to the lectin DBA (uNKDBA+) are known for their angiogenic activity which allows the efficient nutrition of the embryo and the decidua to maintain the homeostasis of the uterine microenvironment during preganancy. Our studies indicate that metyrapone in high concentrations causes miscarriage, whereas at lower doses (0.5mg / ml / kg) it does not change gestational viability. UNK were able to respond to metyrapone treatment in animals fed ad libitum by inducing the genesis of cells expressing low reactivity to lectin DBA (uNKDBAlow) similar to those observed recently in studies involving inflammatory agents such as hyperlipid / hypercaloric diets and e-coli lipopolysaccharide ( LPS). This uNK response is consistent with its angiogenic role and may be important for maintenance of uterine homeostasis after treatment of a glucocorticoid synthesis inhibitor that probably deregulates the HPA axis in these animals. The food restriction caused anxiety-like behavior and impaired the differentiation of uNK DBA + cells, leading to gestational loss of about 75% of the animals submitted to this treatment. Metyrapone did not prevent any of these effects of dietary restriction in pregnant mice