Placental gene expression of the AMPK signaling pathway in association with gestational exposure to ambient air pollution

Abstract

Objective: Prenatal ambient air pollution exposure is able to reach the fetus by crossing the placenta, a highly metabolically active organ. The adenosine monophosphate-activated protein kinase (AMPK) signaling pathway is a crucial regulator of the placental cellular metabolism, necessary for normal placental and fetal development. This study investigates the association between in utero exposure to BC, NO2, and PM2.5, and differences in placental gene expression of the AMPK signaling pathway at birth. Material and methods: Transcription data from 182 placentas of the ENVIRONAGE birth cohort were obtained through microarray analysis. Exposure levels were estimated using a spatio-temporal model for the mothers’ residential address during pregnancy. The associations between transcription levels of 76 genes, clustered by the cascades of the AMPK signaling pathway, and the air pollution exposures during different time windows of pregnancy were analyzed using a mixed-effects model adjusting for potential confounders. Results: Higher prenatal levels of BC, NO2, and PM2.5 were associated with downregulated gene expression of the central AMPK gene cluster and multiple upstream and downstream cascades of the AMPK signaling pathway. In a multi-pollutant model, the observed patterns of downregulation remained, supporting the robustness of the associations when considering co-exposure to different air pollutants. Conclusion: This study provides new insights into the possible adverse effects of ambient air pollution exposure on placental development, affecting the placental metabolism at the transcript level. Whether reduced placental AMPK signaling may play a role in air pollution-induced birth outcomes and their long-term consequences needs to be further addressed.