Grantee Research Project Results

2011 Progress Report: Research Project C: Perinatal Environmental Exposure Disparity and Neonatal Respiratory Health

EPA Grant Number: R833293C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R833293
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: The Center for Study of Neurodevelopment and Improving Children's Health
Center Director: Murphy, Susan K.
Title: Research Project C: Perinatal Environmental Exposure Disparity and Neonatal Respiratory Health
Investigators: Auten, Richard , Foster, W. Michael
Institution: Duke University
EPA Project Officer: Callan, Richard
Project Period: May 1, 2007 through April 30, 2012 (Extended to April 30, 2014)
Project Period Covered by this Report: May 1, 2011 through April 30,2012
RFA: Centers for Children’s Environmental Health and Disease Prevention Research (2005) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

To determine whether maternal exposure to airborne particulates (PM) and/or ozone (1^st hit) restricts fetal growth and/or postnatal growth, and impairs lung development/function in newborn mice;
To determine whether PM and/or ozone exposure re-programs maternal inflammatory responses;
To determine whether postnatal (2^nd hit) ozone exposure further impairs postnatal somatic and lung development/function following maternal PM and/or ozone exposures;
To determine whether genetic or developmental susceptibility to airway hyperreactivity exacerbates maternal and/or postnatal exposure effects on postnatal somatic and lung development/function.

Progress Summary:

For Aim 4, we have distinguished the fetal versus maternal immune responses required for effects of maternal diesel exhaust (or diesel particle instillation) exposure on the induction of fetal pro-inflammatory cytokines in fetal lung, brain, and in placenta.
Our studies on the neural contribution of persistent airway hyperreactivity in newborn mice exposed to environmentally relevant concentrations of ozone have shown that the muscarinic receptor pathway is unaffected, and that the effects are likely relevant to alterations in airway epithelial integrity, since the ozone effects on airway mechanics are apparent with inhaled methacholine challenge, but not apparent with intravenous acetylcholine challenge. The persistence of the epithelial impairment into adulthood well beyond recovery from the intermittent sub-chronic neonatal/juvenile exposures is highly relevant to the potential contribution to susceptibility in adults, which we are now evaluating. We are also examining the afferent neural plasticity in ozone exposed newborns as a potential contributor in collaboration with Dr. David Jacoby at Oregon Health Sciences University. This work has been submitted for publication.
We have tested the contribution of fetal inflammation provoked by maternal diesel inhalation to susceptibility to obesity in adult mice. Diesel exposure of pregnant dams produced obese male offspring reared on a normal diet. If mice were given a high-fat diet, mice born to diesel-exposed dams had more obesity, insulin resistance, and males had higher evidence of anxiety.

Future Activities:

Delineation of the epigenetic mechanisms that underlie the inter-generational burden of perinatal exposure to atmospheric pollutants on juvenile and adult health, in the context of post-natal co-exposures to adverse diet, air pollutants, inflammatory challenges.
Identification of the mechanisms of interaction between co-exposure agents during perinatal life that affect respiratory and cognitive development during juvenile development.
Identify the mechanism underlying the long-term impairment of airway epithelial integrity that follows perinatal and neonatal air pollutant exposures.

Journal Articles on this Report : 3 Displayed | Download in RIS Format

Publications Views
Other subproject views:	All 18 publications	6 publications in selected types	All 6 journal articles
Other center views:	All 163 publications	77 publications in selected types	All 76 journal articles

Publications
Type	Citation	Sub Project	Document Sources
Journal Article	Block ML, Elder A, Auten RL, Bilbo SD, Chen H, Chen J-C, Cory-Slechta DA, Costa D, Diaz-Sanchez D, Dorman DC, Gold DR, Gray K, Jeng HA, Kaufman JD, Kleinman MT, Kirshner A, Lawler C, Miller DS, Nadadur SS, Ritz B, Semmens EO, Tonelli LH, Veronesi B, Wright RO, Wright RJ. The outdoor air pollution and brain health workshop. NeuroToxicology 2012;33(5):972-984.	R833293 (2011) R833293 (2012) R833293 (Final) R833293C003 (2011) R833293C003 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Bolton JL, Smith SH, Huff NC, Gilmour MI, Foster WM, Auten RL, Bilbo SD. Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner. FASEB Journal 2012;26(11):4743-4754.	R833293 (2011) R833293 (Final) R833293C003 (2011) R833293C003 (Final)	Abstract from PubMed Full-text: FASEB-Full Text HTML Exit Abstract: FASEB-Abstract Exit Other: FASEB-Full Text PDF Exit
Journal Article	Miranda ML, Edwards SE, Chang HH, Auten RL. Proximity to roadways and pregnancy outcomes. Journal of Exposure Science & Environmental Epidemiology 2013;23(1):32-38.	R833293 (2011) R833293 (2012) R833293 (Final) R833293C001 (2011) R833293C001 (Final) R833293C002 (2011) R833293C002 (Final) R833293C003 (2011) R833293C003 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: University of Michigan-Full Text PDF Exit Abstract: Nature-Abstract Exit

Supplemental Keywords:

neuroinflammation

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R833293 The Center for Study of Neurodevelopment and Improving Children's Health

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R833293C001 Research Project A: Mapping Disparities in Birth Outcomes
R833293C002 Research Project B: Healthy Pregnancy, Healthy Baby: Studying Racial Disparities in Birth Outcomes
R833293C003 Research Project C: Perinatal Environmental Exposure Disparity and Neonatal Respiratory Health
R833293C004 Community Outreach and Translation Core
R833293C005 Geographic Information System and Statistical Analysis Core

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.