Search

BACKGROUND: Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly. OBJECTIVES: We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes. METHODS: The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina's Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS) in an independent subset of 151 infants. RESULTS: We identified 339 loci with an average methylation difference > 0.125 between any two toenail Hg tertiles. Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS. Ten loci hadp < 0.01 for the association between methylation and the high-risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were hypomethylated in the 16 high-risk profile infants' placentas. Methylation at these loci was moderately correlated (correlation coefficients range, -0.33 to -0.45) with EMID2 expression. CONCLUSIONS: EMID2 hypomethylation may represent a novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral outcomes. [ABSTRACT FROM AUTHOR]

Background Maternal exposure to air pollution is associated with reduced fetal growth, but its relationship with expression of placental imprinted genes (important regulators of fetal growth) has not yet been studied. Objectives To examine relationships between maternal residential air pollution and expression of placental imprinted genes in the Rhode Island Child Health Study (RICHS). Methods Women-infant pairs were enrolled following delivery between 2009 and 2013. We geocoded maternal residential addresses at delivery, estimated daily levels of fine particulate matter (PM 2.5 ; n = 355) and black carbon (BC; n = 336) using spatial-temporal models, and estimated residential distance to nearest major roadway (n = 355). Using linear regression models we investigated the associations between each exposure metric and expression of nine candidate genes previously associated with infant birthweight in RICHS, with secondary analyses of a panel of 108 imprinted genes expressed in the placenta. We also explored effect measure modification by infant sex. Results PM 2.5 and BC were associated with altered expression for seven and one candidate genes, respectively, previously linked with birthweight in this cohort. Adjusting for multiple comparisons, we found that PM 2.5 and BC were associated with changes in expression of 41 and 12 of 108 placental imprinted genes, respectively. Infant sex modified the association between PM 2.5 and expression of CHD7 and between proximity to major roadways and expression of ZDBF2 . Conclusions We found that maternal exposure to residential PM 2.5 and BC was associated with changes in placental imprinted gene expression, which suggests a plausible line of investigation of how air pollution affects fetal growth and development. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence links maternal exposure to particulate matter <2.5 μM in diameter (PM 2.5 ) and deviations in fetal growth. Several studies suggest that the placenta plays a critical role in conveying the effects of maternal PM 2.5 exposure to the developing fetus. These include observed associations between air pollutants and candidate placental features, such as mitochondrial DNA content, DNA methylation and telomere length. However, gaps remain in delineating the pathways linking the placenta to air pollution-related health effects, including a comprehensive profiling of placental processes impacted by maternal PM 2.5 exposure. In this study, we examined alterations in a placental transcriptome-wide network in relation to maternal PM 2.5 exposure prior to and during pregnancy and infant birthweight., Methods: We evaluated PM 2.5 exposure and placental RNA-sequencing data among study participants enrolled in the Rhode Island Child Health Study (RICHS). Daily residential PM 2.5 levels were estimated using a hybrid model incorporating land-use regression and satellite remote sensing data. Distributed lag models were implemented to assess the impact on infant birthweight due to PM 2.5 weekly averages ranging from 12 weeks prior to gestation until birth. Correlations were assessed between PM 2.5 levels averaged across the identified window of susceptibility and a placental transcriptome-wide gene coexpression network previously generated using the WGCNA R package., Results: We identified a sensitive window spanning 12 weeks prior to and 13 weeks into gestation during which maternal PM 2.5 exposure is significantly associated with reduced infant birthweight. Two placental coexpression modules enriched for genes involved in amino acid transport and cellular respiration were correlated with infant birthweight as well as maternal PM 2.5 exposure levels averaged across the identified growth restriction window., Conclusion: Our findings suggest that maternal PM 2.5 exposure may alter placental programming of fetal growth, with potential implications for downstream health effects, including susceptibility to cardiometabolic health outcomes and viral infections., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals., Methods: Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from 34 organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 swabs (bile duct, jejunum, stomach), and 12 stool samples., Results: Pancreatic tissue samples from both sources (RIH and National Disease Research Interchange) had diverse bacterial DNA, including taxa typically identified in the oral cavity. Bacterial DNA across different sites in the pancreas and duodenum were highly subject specific in both cancer and noncancer subjects. Presence of genus Lactobacillus was significantly higher in noncancer subjects compared with cancer subjects and the relative abundance of Fusobacterium spp., previously associated with colorectal cancer, was higher in cancer subjects compared with noncancer subjects., Conclusions: Bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects, regardless of disease state, suggesting that bacteria may be migrating from the gut into the pancreas. Whether bacteria play a causal role in human pancreatic cancer needs to be further examined., Impact: Identifying bacterial taxa that differ in cancer patients can provide new leads on etiologically relevant bacteria., (©2018 American Association for Cancer Research.)