Department of Psychology, University of California - Los Angeles, Los Angeles, CA, United States.
Cousins Center for Psychoneuroimmunology, David Geffen School of Medicine, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences - University of California -Los Angeles, Los Angeles, CA, United States.
Brain Behav Immun. 2019 Feb;76:97-103. doi: 10.1016/j.bbi.2018.11.009. Epub 2018 Nov 14.
Stress exposure is associated with risk for adverse pregnancy outcomes, potentially in part through dysregulated immune and inflammatory activity. Evidence suggests that stress during pregnancy is associated with inflammation during pregnancy, consistent with risk for preterm birth. However, research has not tested whether complementary changes are reflected in immune cell gene expression, or upstream regulation of inflammation. The purpose of this study was to test associations between preconception and prenatal stress exposure and third trimester immune cell gene expression, focusing specifically on sets of genes previously linked to stress in non-pregnant samples: Pro-inflammatory genes, and antiviral and antibody genes.
A sample of 116 low-income, diverse women was recruited from 5 U.S. sites by the Community Child and Health Network at the birth of a child. This study is of the subgroup of women who became pregnant again over the two-year follow-up period, and provided information on stressful life events that occurred both preconception and during the third trimester of the subsequent pregnancy. Dried blood spots (DBS) were collected in the third trimester of pregnancy, and used for gene expression analysis.
Women with more prenatal stressful life events had higher expression of pro-inflammatory genes when compared to those with fewer life events, and the effect was driven by increased activation of pro-inflammatory transcription factors, NF-κB and AP-1. Preconception stressful life event exposure was not associated with gene expression profiles. When entered into models simultaneously, only prenatal stressful life events were associated with up-regulation of pro-inflammatory genes. No differences between high or low stress groups emerged for antiviral or antibody genes.
Prenatal stress exposure was associated with up-regulated pro-inflammatory gene expression during pregnancy, and increased activity of NF-κB and AP-1. In contrast, stress occurring preconception was not associated with gene expression. These results are consistent with the hypothesis that stress-induced activation of pro-inflammatory transcriptional pathways in pregnancy, but not earlier, may increase risk for inflammation-driven adverse pregnancy outcomes.
压力暴露与不良妊娠结局的风险相关，其潜在部分原因可能是免疫和炎症活动失调。有证据表明，孕期压力与孕期炎症相关，这与早产风险一致。然而，研究尚未检验孕期压力是否会反映在免疫细胞基因表达或炎症的上游调节中。本研究旨在检验孕前和孕期压力暴露与孕晚期免疫细胞基因表达之间的关联，特别关注与非孕期样本中压力相关的基因集合：促炎基因、抗病毒和抗体基因。
通过美国五个地点的社区儿童与健康网络，从 116 名低收入、多样化的女性中招募了一个样本，这些女性在孩子出生时参与了研究。本研究是对在两年随访期间再次怀孕的女性亚组进行的研究，提供了在孕前和随后妊娠的第三个孕期发生的应激性生活事件的信息。在妊娠第三个孕期收集了干血斑（DBS），并用于基因表达分析。
与生活事件较少的女性相比，经历较多产前应激性生活事件的女性促炎基因表达更高，其作用是由促炎转录因子 NF-κB 和 AP-1 的激活增加所驱动的。孕前应激性生活事件暴露与基因表达谱无关。当同时纳入模型时，只有产前应激性生活事件与促炎基因的上调相关。高压力组和低压力组之间在抗病毒或抗体基因方面没有差异。
孕期压力暴露与孕期促炎基因表达上调以及 NF-κB 和 AP-1 的活性增加相关。相比之下，发生在孕前的压力与基因表达无关。这些结果与假设一致，即孕期压力诱导的促炎转录途径的激活，而不是更早的激活，可能会增加炎症驱动的不良妊娠结局的风险。
