Baptista Talita, de Azeredo Lucas Araújo, Zaparte Aline, Viola Thiago Wendt, Coral Sayra Catalina, Nagai Maria Aparecida, Mangone Flávia Rotea, Pavanelli Ana Carolina, Schuch Jaqueline B, Mardini Victor, Szobot Claudia M, Grassi-Oliveira Rodrigo
Developmental Cognitive Neuroscience Lab, School of Medicine, Brain Institute of the Rio Grande do Sul (InsCer), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
Discipline of Oncology, Department of Radiology and Oncology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Front Cell Dev Biol. 2021 Jun 4;9:639287. doi: 10.3389/fcell.2021.639287. eCollection 2021.
Prenatal cocaine exposure (PCE) is associated with behavioral, cognitive, and social consequences in children that might persist into later development. However, there are still few data concerning epigenetic mechanisms associated with the effects of gestational cocaine exposure, particularly in human newborns.
We investigated the effects of PCE on DNA methylation patterns of the Oxytocin Receptor () gene in the umbilical cord blood (UCB). The relationship between UCB DNA methylation levels and the severity of the mother's cocaine use during pregnancy was also evaluated.
In this cross-sectional study, 28 UCB samples of newborns with a history of crack cocaine exposure and 30 UCB samples of non-exposed newborns (NEC) were compared for DNA methylation levels at two genomic loci located in exon III of the gene (OXTR1 and OXTR2) through pyrosequencing. Maternal psychopathology was investigated using the Mini International Neuropsychiatric Interview, and substance use characteristics and addiction severity were assessed using the Smoking and Substance Involvement Screening Test (ASSIST).
No differences between newborns with a history of PCE and NEC were observed in OXTR1 or OXTR2 DNA methylation levels. However, regression analyses showed that maternal addiction severity for crack cocaine use predicted OXTR1 DNA methylation in newborns.
These data suggest that methylation levels in the UCB of children are affected by the severity of maternal crack cocaine usage. Larger studies are likely to detect specific changes in DNA methylation relevant to the consequences of PCE.
产前可卡因暴露(PCE)与儿童的行为、认知和社会后果相关,这些后果可能会持续到后期发育阶段。然而,关于与孕期可卡因暴露影响相关的表观遗传机制的数据仍然很少,尤其是在人类新生儿中。
我们研究了产前可卡因暴露对脐带血(UCB)中催产素受体(OXTR)基因DNA甲基化模式的影响。还评估了脐带血DNA甲基化水平与母亲孕期可卡因使用严重程度之间的关系。
在这项横断面研究中,通过焦磷酸测序比较了28例有快克可卡因暴露史的新生儿的脐带血样本和30例未暴露新生儿(NEC)的脐带血样本在OXTR基因外显子III中两个基因组位点(OXTR1和OXTR2)的DNA甲基化水平。使用迷你国际神经精神病学访谈调查母亲的精神病理学情况,并使用吸烟和物质使用参与筛查测试(ASSIST)评估物质使用特征和成瘾严重程度。
在OXTR1或OXTR2 DNA甲基化水平上,有产前可卡因暴露史的新生儿与未暴露新生儿之间未观察到差异。然而,回归分析表明,母亲快克可卡因使用的成瘾严重程度可预测新生儿的OXTR1 DNA甲基化。
这些数据表明,儿童脐带血中的OXTR甲基化水平受母亲快克可卡因使用严重程度的影响。更大规模的研究可能会检测到与产前可卡因暴露后果相关的DNA甲基化的特定变化。