Avaliação de alterações na sinalização estrogênica e inflamatória em placentas de gestantes infectadas com o vírus SARS-CoV-2 no último trimestre de gestação: em busca de marcadores preditivos de transtornos do neurodesenvolvimento

Abstract

INTRODUCTION: Accumulating evidence has shown a significant relationship between viral infections in pregnancy, especially the influenza virus, and increased risk for schizophrenia. Not only the presence of the virus, but the inflammatory process associated with it, is a significant risk factor for the emergence of neurodevelopmental disorders. The blood-placental barrier is more permeable than the blood-brain barrier, allowing the fetus to pass infectious agents and chemicals, such as inflammatory cytokines. In this context, research points to the placenta as a window to the brain, which may provide markers to predict neurodevelopmental disorders. OBJECTIVE: To evaluate possible changes in targets related to estrogen and inflammatory signaling in the placentas of pregnant women infected with the SARS-CoV-2 virus in the last trimester of pregnancy. METHODOLOGY: Pregnant women were recruited in the last trimester of pregnancy, between the 37th and 40th weeks of pregnancy, at the emergency room of the Federal Maternity School Assis Chateaubriand of the Federal University of Ceará. Pregnant women with and without suspected COVID-19 were tested and separated into three groups: control, flu syndrome (GS - with negative RT-PCR for COVID-19), and COVID. After delivery, placentas were collected, dissected, and stored in the laboratory. After dissection, the placenta was divided into maternal (FM) and fetal (FF) sides. So far, we have analyzed the expression of genes of interest in the placentas of 5 pregnant women per group using the RT-PCR technique to determine inflammatory proteins and proteins related to the estrogen signaling pathway. RESULTS: All births were at term, most by cesarean section, no child had low birth weight, most were female, and none had an Apgar score below 8. The results of the mRNA gene expression of the selected markers show that in FM in the COVID group, there was a significant increase in the expression of the proto-oncogene tyrosine-protein kinase (SRC), an intracellular protein activated by estrogen receptors having an important role in embryonic development and cell growth, and in the FF of the nuclear factor kappa B (NF-kB ), a transcription factor for inflammation and oxidative stress, relative to control. Interleukin (IL)-6 tended to increase around 4-fold compared to control in both the SG and COVID groups. CONCLUSION: The results obtained point to the presence of inflammatory changes in the placenta of pregnancies with exposure to the SARS-CoV-2 virus, as well as in the case of IL-6 also related to other respiratory viruses, which points to possible exposure of the fetus to a pro-inflammatory environment being a risk factor for the development of neurodevelopmental disorders.