Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring
Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring
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DOI：
10.1073/pnas.2106115118
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发表时间：
2021-11-23
影响因子：
11.1
通讯作者：
Hurd, Yasmin L.
中科院分区：
文献类型：
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作者：
Rompala, Gregory;Nomura, Yoko;Hurd, Yasmin L.
虽然大麻是怀孕期间使用最多的娱乐性药物之一，但母体使用大麻对胎儿和儿童发育的影响仍不清楚。在这里，我们评估了mCB对幼儿心理社会和生理指标的影响，沿着胎盘转录组中反映的子宫内环境的潜在相关性。儿童（类似于3至6岁）的头发激素水平，神经行为特征的儿童行为评估系统（BASC-2）的调查，心率变异性（HRV）在休息和听觉惊吓。对于进行行为评估的一部分儿童，对出生时收集的胎盘标本进行RNA测序。头发激素分析显示，皮质醇水平增加mCB儿童。此外，mCB与更大的焦虑，侵略性和多动有关。患有mCB的儿童在基线时也表现出HRV高频成分的减少，反映了迷走神经张力的降低。在胎盘中，参与免疫系统功能的许多基因表达减少，包括I型干扰素、中性粒细胞和精氨酸信号通路。最后，这些与mCB相关的免疫基因中有几个组成了与儿童焦虑和多动症相关的共表达网络。总的来说，我们的研究结果揭示了mCB和胎盘中的免疫反应基因网络之间的关系，作为儿童早期焦虑相关问题风险的潜在介导者。
While cannabis is among the most used recreational drugs during pregnancy, the impact of maternal cannabis use (mCB) on fetal and child development remains unclear. Here, we assessed the effects of mCB on psychosocial and physiological measures in young children along with the potential relevance of the in utero environment reflected in the placental transcriptome. Children (similar to 3 to 6 y) were assessed for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children (BASC-2) survey, and heart rate variability (HRV) at rest and during auditory startle. For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing. Hair hormone analysis revealed increased cortisol levels in mCB children. In addition, mCB was associated with greater anxiety, aggression, and hyperactivity. Children with mCB also showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone. In the placenta, there was reduced expression of many genes involved in immune system function including type I interferon, neutrophil, and cytokinesignaling pathways. Finally, several of these mCB-linked immune genes organized into coexpression networks that correlated with child anxiety and hyperactivity. Overall, our findings reveal a relationship between mCB and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood.