Lower Placental Leptin Promoter Methylation in Association with Fine Particulate Matter Air Pollution during Pregnancy and Placental Nitrosative Stress at Birth in the ENVIRONAGE Cohort

Abstract

Background: Particulate matter with a diameter ≤ 2.5 µm (PM2.5) affects human fetaldevelopment during pregnancy. Oxidative stress is a putative mechanism by which PM2.5 mayexert its effects. Leptin (LEP) is an energy regulating hormone involved in fetal growth anddevelopment.Objectives: We investigated in placental tissue whether DNA methylation of the LEP promoteris associated with PM2.5 and whether the oxidative/nitrosative stress biomarker 3-nitrotyrosine (3-NTp) is involved.Methods: LEP DNA methylation status of 361 placentas from the ENVIRONAGE birth cohortwas assessed using bisulfite-PCR-pyrosequencing. Placental 3-NTp (n = 313) was determinedwith an ELISA assay. Daily PM2.5 exposure levels were estimated for each mother’s residence,accounted for residential mobility during pregnancy, using a spatiotemporal interpolation model.Results: After adjustment for a priori chosen covariates, placental LEP methylation was 1.4%lower (95 % CI: -2.7, -0.19%,) in association with an interquartile range increment (7.5 µg/m³) insecond trimester PM2.5 exposure and 0.43% lower (95% CI: -0.85, -0.02%) in association with adoubling of placental 3-NTp content. Conclusions: LEP methylation status in the placenta was negatively associated with PM2.5exposure during the second trimester, and with placental 3-NTp, a marker of oxidative/nitrosativestress. Additional research is needed to confirm our findings and to assess whetheroxidative/nitrosative stress might contribute to associations between PM2.5 and placentalepigenetic events. Potential consequences for health during the neonatal period and later in lifewarrant further exploration.