Alterações epigenéticas do gene do receptor de ocitocina (OXTR) no sangue de cordão umbilical de bebês expostos ao crack durante o desenvolvimento uterino

Abstract

Background: The oxytocin receptor gene (OXTR) shows epigenetic plasticity in response to early life events, especially through of the DNA methylation. In this sense, considering the effects attributed to oxytocin signaling, we highlight the impairment in social and cognitive behaviors displayed by prenatal cocaine exposed (PCE) children. This is particularly relevant given the fact that the cocaine exposure may influence methylation machinery components, lead to changes in the fetal epigenome. Here we investigated the methylation indices in two sequences located in the OXTR exon III gene in umbilical cord blood (UCB) DNA from prenatal crack cocaine newborns and investigate the relationship between methylation levels and maternal crack-cocaine use gravity during pregnancy. Methods: In this cross-sectional study, 29 UCB samples of newborns with a history of crack-cocaine exposure in utero (PCE) and 30 UCB of non-exposed newborns (NEC) were compared for methylation levels in two genomic locus in the exon III of the OXTR gene (OXTR1 and OXTR2) through pyrosequencing. Newborns clinical information was assessed through medical records. Maternal sociodemographic and clinical information was collected using a standardized questionnaire. Maternal psychopathology was investigated using the Mini International Neuropsychiatric and substance use characteristics and addiction severity were assessed with the Smoking and Substance Involvement Screening Test (ASSIST). Results: No differences between PCE and NEC groups were observed in OXTR1 or OXTR2 methylation levels. Regression analyses showed that OXTR2 methylation levels could predict ASSIST scores to crack-cocaine use within PCE group. Conclusion: To our knowledge, this is the first study showing an association between the ASSIST scores and increased levels of OXTR methylation in exon III. Our data suggested that OXTR methylation levels in UCB of children may be affected by maternal crack-cocaine gravity.