Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA; Department of Health Systems and Population Health, School of Public Health, University of Washington, Seattle, WA, USA.
Placenta. 2023 Jul;138:75-82. doi: 10.1016/j.placenta.2023.05.004. Epub 2023 May 14.
Traffic-related air pollution (TRAP), a common exposure, potentially impacts pregnancy through altered placental function. We investigated associations between prenatal TRAP exposure and placental gene expression.
Whole transcriptome sequencing was performed on placental samples from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle and Yakima, WA) (n = 205), cohorts of the ECHO-PATHWAYS Consortium. Residential NO exposures were computed via spatiotemporal models for full-pregnancy, each trimester, and the first/last months of pregnancy. Individual cohort-specific, covariate-adjusted linear models were fit for 10,855 genes and respective exposures (NO or roadway proximity [≤150 m]). Infant-sex/exposure interactions on placental gene expression were tested with interaction terms in separate models. Significance was based on false discovery rate (FDR<0.10).
In GAPPS, final-month NO exposure was positively associated with MAP1LC3C expression (FDR p-value = 0.094). Infant-sex interacted with second-trimester NO on STRIP2 expression (FDR interaction p-value = 0.011, inverse and positive associations among male and female infants, respectively) and roadway proximity on CEBPA expression (FDR interaction p-value = 0.045, inverse among females). In CANDLE, infant-sex interacted with first-trimester and full-pregnancy NO on RASSF7 expression (FDR interaction p-values = 0.067 and 0.013, respectively, positive among male infants and inverse among female infants).
Overall, pregnancy NO exposure and placental gene expression associations were primarily null, with exception of final month NO exposure and placental MAP1LC3C association. We found several interactions of infant sex and TRAP exposures on placental expression of STRIP2, CEBPA, and RASSF7. These highlighted genes suggest influence of TRAP on placental cell proliferation, autophagy, and growth, though additional replication and functional studies are required for validation.
交通相关的空气污染（TRAP）是一种常见的暴露因素，可能通过改变胎盘功能而影响妊娠。我们研究了产前 TRAP 暴露与胎盘基因表达之间的关联。
对 ECHO-PATHWAYS 联盟的 CANDLE（田纳西州孟菲斯）（n=776）和 GAPPS（华盛顿州西雅图和雅基马）（n=205）队列的胎盘样本进行了全转录组测序。通过时空模型计算了整个孕期、每个孕期和孕期前/最后一个月的住宅 NO 暴露。针对每个队列，对 10855 个基因及其各自的暴露因素（NO 或靠近道路[≤150m]）进行了协变量调整的线性模型拟合。通过单独模型中的交互项，测试了胎儿性别/暴露对胎盘基因表达的影响。基于错误发现率（FDR<0.10）进行了显著性检验。
在 GAPPS 中，最后一个月的 NO 暴露与 MAP1LC3C 的表达呈正相关（FDR p 值=0.094）。胎儿性别与第二个孕期的 NO 相互作用影响 STRIP2 的表达（FDR 交互 p 值=0.011，男性和女性婴儿分别呈负相关和正相关），以及与靠近道路的相互作用影响 CEBPA 的表达（FDR 交互 p 值=0.045，女性呈负相关）。在 CANDLE 中，胎儿性别与第一个孕期和整个孕期的 NO 相互作用影响 RASSF7 的表达（FDR 交互 p 值分别为 0.067 和 0.013，男性婴儿呈正相关，女性婴儿呈负相关）。
总体而言，妊娠期间的 NO 暴露与胎盘基因表达的关联主要为阴性，只有最后一个月的 NO 暴露与胎盘 MAP1LC3C 的关联为阳性。我们发现了胎儿性别和 TRAP 暴露对 STRIP2、CEBPA 和 RASSF7 胎盘表达的几个相互作用。这些被强调的基因表明，TRAP 可能对胎盘细胞增殖、自噬和生长有影响，但需要进一步的复制和功能研究来验证。
