PMID- 30125854
OWN - NLM
STAT- MEDLINE
DCOM- 20190313
LR  - 20240405
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Print)
IS  - 0160-4120 (Linking)
VI  - 120
DP  - 2018 Nov
TI  - Intrauterine multi-metal exposure is associated with reduced fetal growth through 
      modulation of the placental gene network.
PG  - 373-381
LID - S0160-4120(18)30986-3 [pii]
LID - 10.1016/j.envint.2018.08.010 [doi]
AB  - BACKGROUND: Intrauterine metal exposures and aberrations in placental processes 
      are known contributors to being born small for gestational age (SGA). However, 
      studies to date have largely focused on independent effects, failing to account 
      for potential interdependence among these markers. OBJECTIVES: We evaluated the 
      inter-relationship between multi-metal indices and placental gene network modules 
      related to SGA status to highlight potential molecular pathways through which in 
      utero multi-metal exposure impacts fetal growth. METHODS: Weighted quantile sum 
      (WQS) regression was performed using a panel of 16 trace metals measured in 
      post-partum maternal toe nails collected from the Rhode Island Child Health Study 
      (RICHS, n = 195), and confirmation of the derived SGA-related multi-metal index 
      was conducted using Bayesian kernel machine regression (BKMR). We leveraged 
      existing placental weighted gene coexpression network data to examine 
      associations between the SGA multi-metal index and placental gene expression. 
      Expression of select genes were assessed using RT-PCR in an independent birth 
      cohort, the New Hampshire Birth Cohort Study (NHBCS, n = 237). RESULTS: We 
      identified a multi-metal index, predominated by arsenic (As) and cadmium (Cd), 
      that was positively associated with SGA status (Odds ratio = 2.73 [1.04, 7.18]). 
      This index was also associated with the expression of placental gene modules 
      involved in "gene expression" (beta = -0.02 [-0.04, -0.01]) and "metabolic hormone 
      secretion" (beta = 0.02 [0.00, 0.05]). We validated the association between cadmium 
      exposure and the expression of GRHL1 and INHBA, genes in the "metabolic hormone 
      secretion" module, in NHBCS. CONCLUSION: We present a novel approach that 
      integrates the application of advanced bioinformatics and biostatistics methods 
      to delineate potential placental pathways through which trace metal exposures 
      impact fetal growth.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Deyssenroth, Maya A
AU  - Deyssenroth MA
AD  - Department of Environmental Medicine and Public Health, Icahn School of Medicine 
      at Mount Sinai, New York, NY 10029, USA.
FAU - Gennings, Chris
AU  - Gennings C
AD  - Department of Environmental Medicine and Public Health, Icahn School of Medicine 
      at Mount Sinai, New York, NY 10029, USA.
FAU - Liu, Shelley H
AU  - Liu SH
AD  - Center for Biostatistics, Department of Population Health Science and Policy, 
      Icahn School of Medicine at Mount Sinai, New York, NY 20019, USA.
FAU - Peng, Shouneng
AU  - Peng S
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Hao, Ke
AU  - Hao K
AD  - Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Lambertini, Luca
AU  - Lambertini L
AD  - Department of Environmental Medicine and Public Health, Icahn School of Medicine 
      at Mount Sinai, New York, NY 10029, USA; Department of Obstetrics, Gynecology and 
      Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA.
FAU - Jackson, Brian P
AU  - Jackson BP
AD  - Department of Earth Sciences, Dartmouth College, Hanover, NH 03755, USA.
FAU - Karagas, Margaret R
AU  - Karagas MR
AD  - Department of Epidemiology, Geisel School of Medicine at Dartmouth, USA.
FAU - Marsit, Carmen J
AU  - Marsit CJ
AD  - Department of Environmental Health, Emory University, Atlanta, GA 30322, USA.
FAU - Chen, Jia
AU  - Chen J
AD  - Department of Environmental Medicine and Public Health, Icahn School of Medicine 
      at Mount Sinai, New York, NY 10029, USA; Department of Pediatrics, Icahn School 
      of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, 
      Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New 
      York, NY 10029, USA; Department of Oncological Sciences, Icahn School of Medicine 
      at Mount Sinai, New York, NY 10029, USA. Electronic address: jia.chen@mssm.edu.
LA  - eng
GR  - R24 ES028507/ES/NIEHS NIH HHS/United States
GR  - R01 ES025145/ES/NIEHS NIH HHS/United States
GR  - UH3 OD023275/OD/NIH HHS/United States
GR  - P42 ES007373/ES/NIEHS NIH HHS/United States
GR  - R01 MH094609/MH/NIMH NIH HHS/United States
GR  - P30 ES023515/ES/NIEHS NIH HHS/United States
GR  - P01 ES022832/ES/NIEHS NIH HHS/United States
GR  - R01 ES029212/ES/NIEHS NIH HHS/United States
GR  - K99 ES029571/ES/NIEHS NIH HHS/United States
GR  - P30 ES019776/ES/NIEHS NIH HHS/United States
GR  - P20 GM104416/GM/NIGMS NIH HHS/United States
GR  - R01 ES022223/ES/NIEHS NIH HHS/United States
GR  - T32 HD049311/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180817
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Environmental Pollutants)
RN  - 0 (GRHL1 protein, human)
RN  - 0 (Metals)
RN  - 0 (Repressor Proteins)
RN  - 0 (inhibin beta A subunit)
RN  - 93443-12-0 (Inhibin-beta Subunits)
SB  - IM
MH  - Adult
MH  - Bayes Theorem
MH  - Birth Weight
MH  - Cohort Studies
MH  - Environmental Pollutants/*analysis
MH  - Female
MH  - *Fetal Development
MH  - Gene Expression Regulation, Developmental
MH  - *Gene Regulatory Networks
MH  - Humans
MH  - Infant, Newborn
MH  - *Infant, Small for Gestational Age
MH  - Inhibin-beta Subunits/genetics
MH  - Male
MH  - Maternal Exposure
MH  - Maternal-Fetal Exchange
MH  - Metals/*analysis
MH  - Nails/chemistry
MH  - Placenta/*metabolism
MH  - Pregnancy
MH  - Repressor Proteins/genetics
PMC - PMC6288802
MID - NIHMS1504064
OTO - NOTNLM
OT  - Birth weight
OT  - Gene coexpression network
OT  - Multi-metal exposure
OT  - Placenta
EDAT- 2018/08/21 06:00
MHDA- 2019/03/14 06:00
PMCR- 2019/11/01
CRDT- 2018/08/21 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/08/01 00:00 [revised]
PHST- 2018/08/03 00:00 [accepted]
PHST- 2018/08/21 06:00 [pubmed]
PHST- 2019/03/14 06:00 [medline]
PHST- 2018/08/21 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - S0160-4120(18)30986-3 [pii]
AID - 10.1016/j.envint.2018.08.010 [doi]
PST - ppublish
SO  - Environ Int. 2018 Nov;120:373-381. doi: 10.1016/j.envint.2018.08.010. Epub 2018 
      Aug 17.