An exploratory analysis of miRNAs measured in placental tissue and their associations with prenatal exposure to household air pollution

Household air pollution (HAP) has been associated with adverse pregnancy and birth outcomes, but the underlying mechanisms remain unclear. Pollutants can cross the placenta, potentially causing dysregulation of the crucial organ. Placental microRNAs (miRNAs) may serve as biomarkers of placental health, but studies of prenatal air pollutant exposure and placental miRNAs using non-targeted approaches have been scarce. We leveraged personal air monitoring data from mothers enrolled in the Ghana Randomized Air Pollution and Health Study to estimate prenatal exposure levels to carbon monoxide (CO) and particulate matter <2.5 µm (PM_2.5). Placental tissue small RNA was sequenced and aligned to miRbase v22. We used sparse principal components analyses (sPCAs) to identify candidate placental miRNAs associated with prenatal CO (<i>N</i> = 133) and PM_2.5 (<i>N</i> = 85) exposure. Associations between candidate miRNAs and prenatal exposures were assessed using linear regressions. We identified four placental miRNAs upregulated with prenatal CO exposure (miR-128-3p, miR-423-3p, miR-671-3p, and miR-744-5p) and five downregulated miRNAs (miR-29b-3p, miR-30e-5p, miR-101-3p, miR-130a-3p, and miR-376b-3p) at <i>P</i> < 0.1. Among female infants only, five miRNAs were downregulated (miR-101-3p, miR-130a-3p, miR-19b-3p, miR-106b-5p, and miR-301a-3p) and one upregulated (miR-22-3) with CO exposure (<i>P</i> < 0.1). We did not identify any associations between placental miRNAs and prenatal PM_2.5 exposure. Our results support associations of prenatal CO exposure with differential expressions of critical placental miRNAs that have been implicated in placental disorders by previous studies. This is the first study to examine associations of these exposures with placental miRNAs using a non-candidate approach and lays the groundwork for targeted studies of placental miRNAs associated with prenatal HAP exposure.