Background

While strong evidence supports adverse maternal and offspring consequences of air pollution, mechanisms that involve the placenta, a key part of the intrauterine environment, are largely unknown. Previous studies of air pollution and placental gene expression were small candidate gene studies that rarely considered prenatal windows of exposure or the potential role of offspring sex. We examined overall and sex-specific associations of prenatal exposure to fine particulate matter (PM_2.5) with genome-wide placental gene expression.

Methods

Participants with placenta samples, collected at birth, and childhood health outcomes from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle, WA) (n = 205) cohorts of the ECHO-PATHWAYS Consortium were included in this study. PM_2.5 exposures during trimesters 1, 2, 3, and the first and last months of pregnancy, were estimated using a spatiotemporal model. Cohort-specific linear adjusted models were fit for each exposure window and expression of >11,000 protein coding genes from paired end RNA sequencing data. Models with interaction terms were used to examine PM_2.5-offspring sex interactions. False discovery rate (FDR < 0.10) was used to correct for multiple testing.

Results

Mean PM_2.5 estimate was 10.5–10.7 μg/m³ for CANDLE and 6.0–6.3 μg/m³ for GAPPS participants. In CANDLE, expression of 13 (11 upregulated and 2 downregulated), 20 (11 upregulated and 9 downregulated) and 3 (2 upregulated and 1 downregulated) genes was associated with PM_2.5 in the first trimester, second trimester, and first month, respectively. While we did not find any statistically significant association, overall, between PM_2.5 and gene expression in GAPPS, we found offspring sex and first month PM_2.5 interaction for DDHD1 expression (positive association among males and inverse association among females). We did not observe PM_2.5 and offspring sex interactions in CANDLE.

Conclusion

In CANDLE, but not GAPPS, we found that prenatal PM_2.5 exposure during the first half of pregnancy is associated with placental gene expression.

中文翻译：

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产前接触颗粒物和胎盘基因表达

背景

虽然强有力的证据支持空气污染对母体和后代的不利影响，但涉及胎盘（宫内环境的关键部分）的机制在很大程度上是未知的。以前对空气污染和胎盘基因表达的研究是小型候选基因研究，很少考虑产前暴露窗口或后代性行为的潜在作用。我们检查了产前细颗粒物 (PM _2.5 ) 暴露与全基因组胎盘基因表达的总体和性别特异性关联。

方法

本研究包括来自 ECHO-PATHWAYS 联盟的 CANDLE（田纳西州孟菲斯）（n = 776）和 GAPPS（华盛顿州西雅图）（n = 205）队列的具有胎盘样本、出生时收集的和儿童健康结果的参与者。使用时空模型估算了妊娠第 1、2、3 个月以及妊娠的第一个月和最后几个月的PM _{2.5暴露量。}队列特异性线性调整模型适用于每个暴露窗口和来自配对末端 RNA 测序数据的 >11,000 个蛋白质编码基因的表达。具有交互项的模型用于检查 PM _2.5 - 后代性交互。错误发现率 (FDR < 0.10) 用于纠正多重测试。

结果

CANDLE的平均 PM _2.5估计值为 10.5–10.7 μg/m ³，GAPPS 参与者的平均 PM 2.5估计值为 6.0–6.3 μg/m ^{3 。}在 CANDLE 中，13 个（11 个上调和 2 个下调）、20 个（11 个上调和 9 个下调）和 3 个（2 个上调和 1 个下调）基因的表达分别与早孕期、中孕期和第一个月的PM _2.5相关. 虽然我们没有发现 PM _2.5和 GAPPS 中的基因表达之间有任何统计学上显着的关联，但我们发现后代性别和第一个月 PM _{2.5相互作用与}DDHD1表达有关（男性之间呈正相关，女性之间呈负相关）。我们没有观察到 PM _2.5和 CANDLE 中的后代性互动。

结论

在 CANDLE 而不是 GAPPS 中，我们发现妊娠前半段的产前 PM _{2.5暴露与胎盘基因表达相关。}