TY - JOUR
T1 - DNA methylation profiles reveal sex-specific associations between gestational exposure to ambient air pollution and placenta cell-type composition in the PRISM cohort study
AU - Saddiki, Hachem
AU - Zhang, Xueying
AU - Colicino, Elena
AU - Wilson, Ander
AU - Kloog, Itai
AU - Wright, Robert O.
AU - Wright, Rosalind J.
AU - Lesseur, Corina
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Background: Gestational exposure to ambient air pollution has been associated with adverse health outcomes for mothers and newborns. The placenta is a central regulator of the in utero environment that orchestrates development and postnatal life via fetal programming. Ambient air pollution contaminants can reach the placenta and have been shown to alter bulk placental tissue DNA methylation patterns. Yet the effect of air pollution on placental cell-type composition has not been examined. We aimed to investigate whether the exposure to ambient air pollution during gestation is associated with placental cell types inferred from DNA methylation profiles. Methods: We leveraged data from 226 mother–infant pairs in the Programming of Intergenerational Stress Mechanisms (PRISM) longitudinal cohort in the Northeastern US. Daily concentrations of fine particulate matter (PM2.5) at 1 km spatial resolution were estimated from a spatiotemporal model developed with satellite data and linked to womens’ addresses during pregnancy and infants’ date of birth. The proportions of six cell types [syncytiotrophoblasts, trophoblasts, stromal, endothelial, Hofbauer and nucleated red blood cells (nRBCs)] were derived from placental tissue 450K DNA methylation array. We applied compositional regression to examine overall changes in placenta cell-type composition related to PM2.5 average by pregnancy trimester. We also investigated the association between PM2.5 and individual cell types using beta regression. All analyses were performed in the overall sample and stratified by infant sex adjusted for covariates. Results: In male infants, first trimester (T1) PM2.5 was associated with changes in placental cell composition (p = 0.03), driven by a decrease [per one PM2.5 interquartile range (IQR)] of 0.037 in the syncytiotrophoblasts proportion (95% confidence interval (CI) [− 0.066, − 0.012]), accompanied by an increase in trophoblasts of 0.033 (95% CI: [0.009, 0.064]). In females, second and third trimester PM2.5 were associated with overall changes in placental cell-type composition (T2: p = 0.040; T3: p = 0.049), with a decrease in the nRBC proportion. Individual cell-type analysis with beta regression showed similar results with an additional association found for third trimester PM2.5 and stromal cells in females (decrease of 0.054, p = 0.024). Conclusion: Gestational exposure to air pollution was associated with placenta cell composition. Further research is needed to corroborate these findings and evaluate their role in PM2.5-related impact in the placenta and consequent fetal programming.
AB - Background: Gestational exposure to ambient air pollution has been associated with adverse health outcomes for mothers and newborns. The placenta is a central regulator of the in utero environment that orchestrates development and postnatal life via fetal programming. Ambient air pollution contaminants can reach the placenta and have been shown to alter bulk placental tissue DNA methylation patterns. Yet the effect of air pollution on placental cell-type composition has not been examined. We aimed to investigate whether the exposure to ambient air pollution during gestation is associated with placental cell types inferred from DNA methylation profiles. Methods: We leveraged data from 226 mother–infant pairs in the Programming of Intergenerational Stress Mechanisms (PRISM) longitudinal cohort in the Northeastern US. Daily concentrations of fine particulate matter (PM2.5) at 1 km spatial resolution were estimated from a spatiotemporal model developed with satellite data and linked to womens’ addresses during pregnancy and infants’ date of birth. The proportions of six cell types [syncytiotrophoblasts, trophoblasts, stromal, endothelial, Hofbauer and nucleated red blood cells (nRBCs)] were derived from placental tissue 450K DNA methylation array. We applied compositional regression to examine overall changes in placenta cell-type composition related to PM2.5 average by pregnancy trimester. We also investigated the association between PM2.5 and individual cell types using beta regression. All analyses were performed in the overall sample and stratified by infant sex adjusted for covariates. Results: In male infants, first trimester (T1) PM2.5 was associated with changes in placental cell composition (p = 0.03), driven by a decrease [per one PM2.5 interquartile range (IQR)] of 0.037 in the syncytiotrophoblasts proportion (95% confidence interval (CI) [− 0.066, − 0.012]), accompanied by an increase in trophoblasts of 0.033 (95% CI: [0.009, 0.064]). In females, second and third trimester PM2.5 were associated with overall changes in placental cell-type composition (T2: p = 0.040; T3: p = 0.049), with a decrease in the nRBC proportion. Individual cell-type analysis with beta regression showed similar results with an additional association found for third trimester PM2.5 and stromal cells in females (decrease of 0.054, p = 0.024). Conclusion: Gestational exposure to air pollution was associated with placenta cell composition. Further research is needed to corroborate these findings and evaluate their role in PM2.5-related impact in the placenta and consequent fetal programming.
KW - Cell types
KW - Compositional regression
KW - DNA methylation
KW - Fine particulate matter
KW - Placenta
UR - http://www.scopus.com/inward/record.url?scp=85178171156&partnerID=8YFLogxK
U2 - 10.1186/s13148-023-01601-x
DO - 10.1186/s13148-023-01601-x
M3 - Article
C2 - 38041176
AN - SCOPUS:85178171156
SN - 1868-7075
VL - 15
JO - Clinical Epigenetics
JF - Clinical Epigenetics
IS - 1
M1 - 188
ER -
