2017 Progress Report: Neurodevelopment and Improving Children's Health following EtS exposure (NICHES)

EPA Grant Number: R835437
Center: The Center for Study of Neurodevelopment and Improving Children's Health
Center Director: Murphy, Susan K.
Title: Neurodevelopment and Improving Children's Health following EtS exposure (NICHES)
Investigators: Murphy, Susan K. , Fuemmeler, Bernard , Hoyo, Cathrine , Kollins, Scott H , Levin, Edward D , Satterwhite, Lisa , Schechter, Julia , Seidler, Frederick , Slotkin, Theodore , Wylie, Jamie
Institution: Duke University
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: June 1, 2013 through May 31, 2018 (Extended to May 31, 2019)
Project Period Covered by this Report: June 1, 2017 through May 31,2018
Project Amount: $3,907,780
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2012) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

Project 1 is examining the relationship between smoke exposure during early life and neurobehavioral outcomes in children followed from prior to birth through up to age 7 years, with a particular focus on attention-deficit/hyperactivity disorder (ADHD). This project also is examining the relationship between smoke exposure, ADHD and DNA methylation.

Project 2 is determining how exposure during early development to tobacco smoke extract (TSE) and to nicotine influences growth and neurobehavioral outcomes in rats and neural differentiation and neurotransmitter phenotypes in vitro. This project also is working to define the most sensitive developmental window(s) of vulnerability to tobacco smoke and nicotine exposure and will determine if dietary interventions can ameliorate the effects of these exposures.

Project 3 is investigating how in utero tobacco smoke and nicotine exposure in rats influences DNA methylation in the brain and blood, and how the methylation profiles in the brain relate to gene expression. These findings are being applied to the study of cord blood from our human cohort to determine if methylation patterns can be used to stratify the risk of ADHD prior to the onset of symptoms. ADHD-associated genes also will be examined in the in vitro models of neurodifferentiation and neurotransmission to determine associations with these phenotypes.

Progress Summary:

Project 1

Our objective is to evaluate the associations of both environmental tobacco smoke (ETS) exposure on cognitive and neurobehavioral outcomes across early development and to examine the role of exposure-induced DNA methylation changes on these outcomes.

Aim 1: Characterize the extent and developmental timing of ETS exposure effects on cognitive and neurobehavioral outcomes in young children.

Aim 2: Determine the relation between DNA methylation and cognitive and neurobehavioral outcomes in young children.

Progress Summary: During our 5th year, we have made steady progress in recruitment. Since study initiation, there were approximately 1,195 participants in our cohort who met our inclusion criteria. Of these, 170 have since refused or moved out of our catchment area, leaving 714 women and their 5-13 year old children eligible. We have enrolled 311 participants: 60.8 percent African American, 31.8 percent Caucasian, 5.8 percent multiracial, 1.3 percent Asian and 0.3 percent other or unknown race. Hispanics are underrepresented in our cohort, because English language was a requirement of participation since we do not have a Spanish-language protocol or sufficient staff who are able to administer the protocol in Spanish. The mean age for children at the time of our enrollment (time 1) is 5.6 years (SD = 2.01, range = 3-11). The mean age for children at time 2 is 7 years (SD = 1.2, range = 5-9). We are reaching out to the remaining participants through mail, scheduled recruitment events, or meeting them during well-child clinic visits in order to enroll them for NICHES.

We have completed baseline neurodevelopmental assessments of 311 mother-child dyads, and 156 of these have completed their 2-year follow-up assessments. For both mothers and their children, this includes, among other parent-report survey measures, assessments of executive functioning using the National Institutes of Health (NIH) Toolbox and an IQ test. Among these children, we have collected saliva from nearly every participant (296 individual saliva samples at time 1 and 150 saliva samples at time 2), which will provide a method for assessing cotinine and potentially DNA methylation. Obtaining blood samples has been much more difficult, given that many children have refused this aspect of the protocol. To make it easier, we have been offering capillary or venipuncture draw. Overall, we have collected blood on 61 participants at time 1 (42 via venipuncture and 19 via capillary) and 38 participants at time 2 (3 via venipuncture and 35 via capillary). In the past year, we have assayed a batch of collected saliva samples for cotinine and have presented findings at conferences from these assays. During the no-cost extension (NCE), we plan to analyze children's saliva and blood samples for DNA methylation in selected differentially methylated regions of interest. Loci chosen will be informed through putative pathways, recent findings in the literature, and findings from Projects 2 and 3. The main goal of these analyses will be to assess the stability of epigenetic loci related to smoke exposure or predictive of attention and cognition from birth through childhood.

Our current battery of neurodevelopmental tests for the child and mother participants include the NIH Toolbox with eight tasks; the Differential Abilities Scale (DAS) with four to six subtests; Wechsler Abbreviated Scale of Intelligence–II (WASI) with four subtests; and parent self-report measures that include the Conner's Adult ADHD Rating Scales (CAARS), Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN), Strengths and Difficulties Questionnaire (SDQ), Behavior Rating Inventory of Executive Function (BRIEF), Behavior Assessment System for Children (BASC) and Parent Stress Index (PSI). During this report period, we have completed the full battery of tests on the entire 311 mother and child dyads who completed study visits.

During this reporting period, we also have published several manuscripts detailing some of the findings from NICHES and have presented preliminary results at multiple conferences. For example, in January 2018, we published an article examining the impact of a statewide smoking ban on cotinine levels during pregnancy, and this article was featured on several news outlets and chosen as the National Institute of Environmental Health Sciences Extramural Paper of the Month. In March 2018, we published a study in Brain, Behavior, and Immunity looking at the association between maternal cytokine levels and child neurodevelopmental outcomes. We have several manuscripts under review, including one examining the interaction between cotinine and depressive symptoms in predicting birthweight, as well as several manuscripts in preparation, including one looking at the associations between prenatal and postnatal cotinine and neurodevelopmental outcomes and another examining social-emotional behaviors measured between 12-24 months predicting ADHD symptoms in children ages 4-7. We also presented data at several conferences this year, including presentations looking at the sensitivity and specificity of questions asking parents about secondhand smoke exposure compared to children's cotinine levels and their family's home policies regarding smoking compared to children's cotinine levels. We plan to write manuscripts detailing these results for publication later in the year.

Significance: This study will add data on the effects of secondhand smoke exposure on child cognitive development and identify potential epigenetic signatures mediating these associations.

Project 2

Progress Summary: Project 2 is determining how exposure during early development to tobacco smoke extract and to nicotine influences growth and neurobehavioral outcomes in rats and neural differentiation and neurotransmitter phenotypes in vitro. This project also is working to define the most sensitive developmental window(s) of vulnerability to tobacco smoke and nicotine exposure, which components of tobacco smoke are driving the effects and whether dietary interventions can ameliorate the effects of these exposures.

Aim 1. Determine the behavioral phenotypes resulting from developmental nicotine and ETS exposure.

Aim 2. Determine the deficits in specific neural circuits that cause the behavioral anomalies: in vivo neurochemistry (Slotkin and Seidler)

Aim 3. Determine cellular and molecular mechanisms for nicotine/tobacco extract-induced developmental neurotoxicity

In Project 2 we are determining with rat models and cell lines the behavioral consequences of developmental exposure to tobacco smoke constituents and the neural mechanisms.

For the in vivo work, we completed and published the behavioral results from a major study, which compared the long-term behavioral effects of gestational TSE modeling environmental tobacco smoke exposure (secondhand smoke) with the same amount of nicotine alone (0.2 mg/kg/day) or 10 times that nicotine level (2 mg/kg/day) modeling the nicotine exposure of primary smoking. These results were published in Toxicological Sciences (Hall et al., 2016). The neurochemical results from this study were published previously by our group (Slotkin et al., 2015).

We completed a second major study of the critical windows of exposure (preconception, early gestation and late gestation) to TSE. The neurochemical results have been published in Toxicological Sciences (Slotkin et al., 2016a). The behavioral results from this study have been presented at scientific meetings and will be submitted imminently for peer review publication.

We finished the study of key neural systems and sex differences in cognitive function under a supplement to the center. This study found that hippocampal muscarinic cholinergic systems were differentially involved in the spatial memory function of male and female rats. This has been published in Neuropharmacology (Hall et al., 2017). We are midway through a study of the interaction between two principal "bad actors" in TSE, nicotine and the polyaromatic hydrocarbon benzo-a-pyrene (BaP). We are now initiating a study of how TSE-induced locomotor hyperactivity might be reversed with therapeutic drug treatment.

With our in vitro studies, we found that adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinepherine (Slotkin et al., 2016b), and we identified two principal vulnerable points for brain maturation: differentiation of cells into neurons and glia, and differentiation of neurons into cholinergic and monoaminergic transmitter. We discovered that different TSE components affect different ones of these processes (Slotkin et al., 2016c). Studies with human neural stem cells are ongoing, testing the adverse impacts of TSE and potential treatments to attenuate the cytotoxic impacts.

Satterwhite's group developed a unique in vitro stem cell model of human neurodevelopment for NICHES and used this model to define molecular mechanisms of neurodevelopmental toxicity and to characterize remediation strategies. NIH-approved WA01 (male) and WA09 (female) embryonic stem cells (WiCell) were differentiated to hNSCs, and culture conditions developed to produce neurons, astrocytes and oligodendrocytes. Major advantages of the human embryonic stem cell sourced model are that (1) cell proliferation and differentiation can be studied in the same cells, (2) in vitro molecular phenotypes can be compared directly with human blood and brain samples, and (3) molecular mechanism of candidate remediation strategies can be screened before clinical studies.

Significance: The rat studies show the cause-and-effect relationship between developmental exposure to the complex mixture of tobacco smoke and two principal neurotoxic components, nicotine and BaP, with regard to locomotor hyperactivity as well as cognitive impairment in the novel object recognition test with the TSE causing a more substantial effect than nicotine alone. Analysis of the critical windows of exposure showed that late gestational exposure to the tobacco smoke extract caused the most substantial neurochemical and neurobehavioral effects but that persistent impairments were seen after early gestational and even premating exposure. The in vivo and neurochemical studies demonstrated that the same TSE exposure disrupted dopaminergic, serotonergic and cholinergic neurotransmitter systems with greater effects of the tobacco constituent mixture compared with nicotine alone. In addition to nicotine, a critical bad actor in the TSE was the polyaromatic hydrocarbon BaP. Developmental exposure of rats to a low dose (0.03 mg/kg/day throughout gestation) of BaP caused a significant reversal of a normal sex difference in locomotor activity in which female rats are normally more active than male rats. Prenatal BaP exposure causes a hyperactivity in males but not females, eliminating the normal sex difference in locomotor behavior. Sex-selective effects also are seen with nicotine and BaP exposures in emotional and cognitive tests. Low-dose developmental exposure can cause long-lasting diminution of these normal sex differences. BaP also caused a significant impairment in the percent hit performance on the attentional test in male but not female offspring. The in vitro studies showed cellular disruptions of proliferation and differentiation again with the tobacco constituent mixture causing more pervasive effects than the same concentration of nicotine alone. The human neural stem cells are more sensitive to both nicotine and TSE than the rat PC12 cells and provide an opportunity to establish direct concordance between human clinical samples (Project 1) and in vitro exposure phenotypes (Project 2).

Project 3

Aim 1: Identify ETS-related methylation targets.

Aim 2: Identify ETS-altered methylation-expression relationships in frontal cortex.

Aim 3: Determine if DNA methylation varies with ETS dose in humans.

Progress Summary: Over the last reporting period, we contracted with the Duke Biostatistics and Bioinformatics Resource to perform analysis of our previously generated whole genome bisulfite sequencing (WGBS) data from the rats exposed in utero to nicotine at two concentrations (mother's exposure levels: 0.2 mg/kg/day or 2 mg/kg/day) or tobacco smoke extract with mother's exposure level of the nicotine contained within the extract at 0.2 mg/kg/day (Specific Aim 1). We generated WGBS data for two regions of the brain (hippocampus and frontal cortex) and peripheral blood. We contracted with this Duke core facility (Dr. David Corcoran supervised the analysis) because the Master's student who had been working on this had insufficient time (due to other responsibilities) to complete the work. The analysis has now been completed. In addition, the transcriptome data generated from the same tissues (except for peripheral blood) also have been analyzed, and the data from the WGBS and RNA-Seq have been integrated (Specific Aim 2). In the NCE funding period, we will identify and validate top targets for confirmation and further analysis in the human cohort from Project 1 (Specific Aim 3) and the exposed and control rats from Project 2. Cotinine levels were generated from the mother's blood collected at the time of recruitment (early pregnancy), and these data have been used in several projects described above. We submitted samples from our human cohort for determination of lead levels, as well as a suite of approximately 30 other metals, and are awaiting receipt of the final results. These data will help us to adjust for lead exposure as a potential contributor to the development of ADHD.

We are awaiting final analysis results from the Duke Biostatistics and Bioinformatics Core for reduced representation bisulfite sequencing data generated from a subset of our study participants' cord blood, having selected a group with relative high maternal cotinine levels and those with very low level cotinine levels for direct comparisons. These data represent comprehensive methylation data for cord blood of infants exposed to tobacco smoke versus controls and also will provide a baseline for us to compare against the results from the rat and potentially provide additional novel differentially methylated targets to pursue in the human cohort.

Significance: These results address the influence of a single exposure (nicotine) and a complex mixture (TSE) during in utero development on the hippocampus, frontal cortex and peripheral blood epigenome of the offspring and provide for determining functional relevance of the DNA methylation changes in the brain, as well as methylation profiles that are consistent between blood and brain, suggestive of an effect occurring in very early development (before specification of the germ layers). Furthermore, we have developed comprehensive DNA methylation data for a subset of our human cohort for whom we have neurobehavioral developmental assessments and objective measurements of exposure, allowing us to determine potential relationships between exposure in humans, epigenetic alterations and developmental outcomes.

Future Activities:

Project 1

During our no-cost extension, we will (1) complete participant enrollment and follow-up visits, (2) conduct assays of stored specimens in preparation of scientific products, and (3) complete final manuscripts related to the primary aims, as well as ancillary ones being led by our students and affiliated investigators.

  1. Complete participant recruitment and study follow-up visits. We have completed baseline neurodevelopmental assessments of 311 mother-child dyads, and 156 of these have completed their 2-year follow-up assessments. We plan to enroll an additional 49 participants within the next year and continue followup with our currently enrolled participants. We also will collect specimen samples (saliva, blood and teeth) from each willing participant for assays of cotinine, lead, epigenetics and other biomarkers. Our goal of 49 participants will yield a final enrolled sample of 360. This sample size has been adjusted to reflect delays in recruitment due to an administrative hold, as well as the hiring and training of new research staff.
  2. Conduct assays of stored specimens. We will complete assays of cotinine for all participants enrolled and followed during the NCE period. We also will use the final year to complete assays of DNA methylation among selected regulatory gene regions. CpG regions chosen will be informed through putative pathways, recent findings in the literature, and findings from Projects 2 and 3. We will determine the extent to which these gene regions are associated with prenatal smoke exposure and if they also relate to neurodevelopmental ADHD-related symptoms and cognitive problems. In addition, for those that are significantly associated with exposure or outcomes, we will evaluate their temporal stability using stored blood specimens collected at the follow-up visits.

Project 2

With the most sensitive neurobehavioral effect (locomotor hyperactivity), we will test therapeutic pharmacotherapies to attenuate the neurobehavioral dysfunction caused by TSE and nicotine exposure during development.

Project 3

From our multiple 'omics-level data, we will work to validate differential methylation of genes, prioritizing genes showing a functional relationship between DNA methylation and expression in the brains of rats and determining relationships between the methylation and behavioral data from Project 2. We also will validate genes showing differential methylation in humans and determine relationships between methylation in cord blood, exposure to tobacco smoke in utero and developmental outcomes as measured in Project 1.


Journal Articles: 33 Displayed | Download in RIS Format

Other center views: All 116 publications 38 publications in selected types All 33 journal articles
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Journal Article Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Hussey Freeland DM, Miller R, Murphy SK. Small-magnitude effect sizes in epigenetic end points are important in children’s environmental health studies: the Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group. Environmental Health Perspectives 2017;125(4):511-526. R835437 (2017)
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  • Journal Article Cauley M, Hall BJ, Abreu-Villaca Y, Junaid S, White H, Kiany A, Slotkin TA, Levin ED. Critical developmental periods for effects of low-level tobacco smoke exposure on behavioral performance. Neurotoxicology 2018;68:81-87. R835437 (2017)
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  • Journal Article Fuemmeler BF, Wang L, Iversen ES, Maguire R, Murphy SK, Hoyo C. Association between prepregnancy body mass index and gestational weight gain with size, tempo, and velocity of infant growth: analysis of the Newborn Epigenetic Study cohort. Childhood Obesity 2016;12(3):210-218. R835437 (2015)
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  • Journal Article Fuemmeler BF, Lee CT, Soubry A, Iversen ES, Huang Z, Murtha AP, Schildkraut JP, Jirtle RL, Murphy SK, Hoyo C. DNA methylation of regulatory regions of imprinted genes at birth and its relation to infant temperament. Genetics and Epigenetics 2016;8:59-67. R835437 (2017)
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  • Journal Article Gao L, Liu X, Millstein J, Siegmund KD, Dubeau L, Maguire RL, Zhang JJ, Fuemmeler BF, Kollins SH, Hoyo C, Murphy SK, Breton CV. Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes. Clinical Epigenetics 2018;10(1):98 (11 pp.). R835437 (2017)
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  • Journal Article Hall BJ, Cauley M, Burke D, Kiany A, Slotkin TA, Levin ED. Cognitive and behavioral impairments evoked by low-level exposure to tobacco smoke components: comparison with nicotine alone. Toxicological Sciences 2016;151(2):236-244. R835437 (2015)
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  • Journal Article Hall BJ, Abreu-Villaca Y, Cauley M, Junaid S, White H, Kiany A, Levin ED. The ventral hippocampal muscarinic cholinergic system plays a key role in sexual dimorphisms of spatial working memory in rats. Neuropharmacology 2017;117:106-113. R835437 (2017)
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  • Journal Article King KE, Kane JB, Scarbrough P, Hoyo C, Murphy SK. Neighborhood and family environment of expectant mothers may influence prenatal programming of adult cancer risk: discussion and an illustrative DNA methylation example. Biodemography and Social Biology 2016;62(1):87-104. R835437 (2015)
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  • Journal Article Levin ED. Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery. Neurotoxicology and Teratology 2015;52(Pt A):88-92. R835437 (2014)
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  • Journal Article Murphy SK, Erginer E, Huang Z, Visco Z, Hoyo C. Genotype-epigenotype interaction at the IGF2 DMR. Genes 2015;6(3):777-789. R835437 (2014)
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  • Journal Article Nye MD, Fry RC, Hoyo C, Murphy SK. Investigating epigenetic effects of prenatal exposure to toxic metals in newborns: challenges and benefits. Medical Epigenetics 2014;2(1):53-59. R835437 (2013)
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  • Journal Article Nye MD, Hoyo C, Murphy SK. In vitro lead exposure changes DNA methylation and expression of IGF2 and PEG1/MEST. Toxicology In Vitro 2015;29(3):544-550. R835437 (2014)
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  • Journal Article Nye MD, King KE, Darrah TH, Maguire R, Jima DD, Huang Z, Mendez MA, Fry RC, Jirtle RL, Murphy SK, Hoyo C. Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort. Environmental Epigenetics 2016;2(1):1-8. R835437 (2015)
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  • Journal Article Schechter JC, Kollins SH. Prenatal smoke exposure and ADHD: advancing the field. Pediatrics 2017;139(2):e20163481 (2 pp.). R835437 (2017)
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  • Journal Article Schechter JC, Fuemmeler, BF, Hoyo C, Murphy SK, Zhang JJ, Kollins SH. Impact of smoking ban on passive smoke exposure in pregnant non-smokers: using cotinine as a biomarker of exposure. International Journal of Environmental Research and Public Health 2018;15(1):E83 (16 pp.). R835437 (2017)
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  • Journal Article Slotkin TA, Card J, Seidler FJ. Adverse benzo[a]pyrene effects on neurodifferentiation are altered by other neurotoxicant coexposures: interactions with dexamethasone, chlorpyrifos, or nicotine in PC12 cells. Environmental Health Perspectives 2013;121(7):825-831. R835437 (2013)
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  • Journal Article Slotkin TA, Card J, Seidler FJ. Nicotine administration in adolescence reprograms the subsequent response to nicotine treatment and withdrawal in adulthood: sex-selective effects on cerebrocortical serotonergic function. Brain Research Bulletin 2014;102:1-8. R835437 (2014)
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  • Journal Article Slotkin TA, Card J, Stadler A, Levin ED, Seidler FJ. Effects of tobacco smoke on PC12 cell neurodifferentiation are distinct from those of nicotine or benzo[a]pyrene. Neurotoxicology and Teratology 2014;43:19-24. R835437 (2013)
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  • Journal Article Slotkin TA, Skavicus S, Card J, Levin ED, Seidler FJ. Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: nicotinic receptor blockade, antioxidants, methyl donors. Toxicology 2015;333:63-75. R835437 (2014)
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  • Journal Article Slotkin TA, Skavicus S, Card J, Stadler A, Levin ED, Seidler FJ. Developmental neurotoxicity of tobacco smoke directed toward cholinergic and serotonergic systems: more than just nicotine. Toxicological Sciences 2015;147(1):178-189. R835437 (2014)
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  • Journal Article Slotkin TA, Stadler A, Skavicus S, Seidler FJ. Adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinephrine. Brain Research Bulletin 2016;122:71-75. R835437 (2015)
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  • Journal Article Slotkin TA, Skavicus S, Card J, Levin ED, Seidler FJ. Diverse neurotoxicants target the differentiation of embryonic neural stem cells into neuronal and glial phenotypes. Toxicology 2016;372:42-51. R835437 (2016)
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  • Journal Article Slotkin TA, Stadler A, Skavicus S, Card J, Ruff J, Levin ED, Seidler FJ. Is there a critical period for the developmental neurotoxicity of low-level tobacco smoke exposure? Toxicological Sciences 2017;155(1):75-84. R835437 (2017)
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  • Journal Article Slotkin, T.A., Stadler, A., Skavicus, S., Card, J., Ruff, J., Levin, E.D., Seidler, F.J. 2016. Is there a critical period for the developmental neurotoxicity of low-level tobacco smoke exposure? Toxicological Sciences. DOW:10.1093. R835437 (2016)
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    Journal Article Smeester L, Yosim AE, Nye MD, Hoyo C, Murphy SK, Fry RC. Imprinted genes and the environment: links to the toxic metals arsenic, cadmium, lead and mercury. Genes 2014;5(2):477-496. R835437 (2014)
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  • Journal Article Soubry A, Hoyo C, Jirtle RL, Murphy SK. A paternal environmental legacy: evidence for epigenetic inheritance through the male germ line. BioEssays 2014;36(4):359-371. R835437 (2013)
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  • Journal Article Tindula G, Murphy SK, Grenier C, Huang Z, Huen K, Escudero-Fung M, Bradman A, Eskenazi B, Hoyo C, Holland N. DNA methylation of imprinted genes in Mexican-American newborn children with prenatal phthalate exposure. Epigenomics 2018;10(7):1011-1026. R835437 (2017)
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  • Journal Article Vidal AC, Benjamin Neelon SE, Liu Y, Tuli AM, Fuemmeler BF, Hoyo C, Murtha AP, Huang Z, Schildkraut J, Overcash F, Kurtzberg J, Jirtle RL, Iversen ES, Murphy SK. Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans. Genetics and Epigenetics 2014;6:37-44. R835437 (2014)
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  • Journal Article Lee, W.-C., Shen, L., Catalano, P.J., Mickley, L.J., and Koutrakis, P. (2017). Effects of Future Temperature Change on PM2.5 Infiltration in the Greater Boston Area. Atmospheric Environment 150, 98-105. R835437 (2016)
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    Journal Article Carrie V. Breton, Carmen J. Marsit, Elaine Faustman, Kari Nadeau, Jaclyn M. Goodrich, Dana C. Dolinoy, Julie Herbstman, Nina Holland, Janine M. LaSalle, Rebecca Schmidt, Paul Yousefi, Frederica Perera, Bonnie R. Joubert, Joseph Wiemels, Michele Taylor, Ivana V. Yang, Rui Chen, Kinjal M. Hew, Deborah M. Hussey Freeland, Rachel Miller, and Susan K. Murphy. 2017. Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children’s Environmental Health Studies:The Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group. Environmental Health Perspectives. 2017:125(4) 511-526. R835437 (2016)
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    Journal Article Levin ED and Y Abreu-Villaça. Developmental neurotoxicity of nicotine and tobacco. In Handbook of Developmental Neurotoxicology, (C. Wang, M. Paule, and W. Slikker, Jr. eds.), Academic Press, San Diego, 2017. R835437 (2016)
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    Journal Article Fleisch, A.F., Kloog, I., Luttmann-Gibson, H., Gold, D.R., Oken, E., and Schwartz, J.D. (2016). Air Pollution Exposure and Gestational Diabetes Mellitus Among Pregnant Women in Massachusetts:a Cohort Study. Environmental Health 15, 1-9. R835437 (2016)
    R834798C005 (Final)
    not available
    Journal Article Breton, C.V., Marsit, C.J., Faustman, E., Nadeau, K., Goodrich, J.M., Dolinoy, D.C., Herbstman, J., Holland, N., LaSalle, J.M., Schmidt, R., Yousefi, P., Perera, F., Joubert, B.R., Wiemels, J., Taylor, M., Yang, I.V., Chen, R., Hew, K.M., Hussey Freeland, D.M.,Miller, R. and S.K. Murphy. 2016. Small Magnitude Effect Sizes in Epigenetic Endpoints are Important in Children's Environmental Health Studies:The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives (in press) DOI:10.1289/EHP595. R835437 (2016)
    not available

    Supplemental Keywords:

    NICHES WebsiteSecondhand smoke, nicotine, tobacco smoke extract, attention-deficit/hyperactivity disorder, ADHD, neurobehavior, cognitive function, neurotransmission, human neural stem cells, pyrosequencing, DNA methylation, epigenetics, Instagram

    Relevant Websites:

    NICHES website: Exit

    Welcome to "Help Babies Not Smoke" Exit

    Progress and Final Reports:

    Original Abstract
  • 2013 Progress Report
  • 2014 Progress Report
  • 2015 Progress Report
  • 2016 Progress Report