Abstract
Exposure to ambient air pollution during pregnancy has been associated with an increased risk of preeclampsia (PE). Some suggested mechanisms behind this association are changes in placental DNA methylation and gene expression. The objective of this study was to identify how early pregnancy exposure to ambient nitrogen oxides (NOx) among PE cases and normotensive controls influence DNA methylation (EPIC array) and gene expression (RNA-seq). The study included placentas from 111 women (29 PE cases/82 controls) in Scania, Sweden. First-trimester NOx exposure was assessed at the participants’ residence using a dispersion model and categorized via median split into high or low NOx. Placental gestational epigenetic age was derived from the DNA methylation data. We identified six differentially methylated positions (DMPs, q < 0.05) comparing controls with low NOx vs. cases with high NOx and 14 DMPs comparing cases and controls with high NOx. Placentas with female fetuses showed more DMPs (N = 309) than male-derived placentas (N = 1). Placentas from PE cases with high NOx demonstrated gestational age deceleration compared to controls with low NOx (p = 0.034). No differentially expressed genes (DEGs, q < 0.05) were found. In conclusion, early pregnancy exposure to NOx affected placental DNA methylation in PE, resulting in placental immaturity and showing sexual dimorphism.
Highlights
Preeclampsia (PE) affects, in average, 0.2%–9% of pregnancies worldwide [1,2] and has been associated with increased risk of maternal mortality [3,4] and maternal cardiovascular disease (CVD) in later life
We summarized the descriptive data of the participants and evaluated differences in characteristics between PE cases and controls using the χ2 test for categorical variables and a t-test for continuous variables (Table 1)
We investigated whether the combined PE status and nitrogen oxides (NOx) exposure group was associated with differential methylation of specific positions in the genome
Summary
Preeclampsia (PE) affects, in average, 0.2%–9% of pregnancies worldwide [1,2] and has been associated with increased risk of maternal mortality [3,4] and maternal cardiovascular disease (CVD) in later life. Preeclampsia presents with new onset hypertension after 20 weeks of gestation accompanied by proteinuria and/or dysfunction of one or more maternal organs [7]. Preeclampsia is commonly divided into early-onset PE (manifesting before week 34) and late-onset PE (at or after 34 weeks) [9]. Early-onset PE is characterized by poor placentation and higher maternal and fetal morbidity and mortality. Late-onset PE makes up 80% of the PE cases and is associated with maternal risk factors such as metabolic syndrome, obesity, and impaired glucose tolerance. Studies have implicated that a female fetus is more common in early-onset PE [10] and a male fetus in late-onset PE [11]
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