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https://www.readbyqxmd.com/read/27824486/novel-epigenetic-biomarkers-mediating-bisphenol-a-exposure-and-metabolic-phenotypes-in-female-mice
#1
Olivia S Anderson, Jung H Kim, Karen E Peterson, Brisa N Sanchez, Karilyn E Sant, Maureen A Sartor, Caren Weinhouse, Dana C Dolinoy
There is compelling evidence that epigenetic modifications link developmental environmental insults to adult disease susceptibility. Animal studies have associated perinatal bisphenol A (BPA) exposure to altered DNA methylation, but these studies are often limited to candidate gene and global non-loci specific approaches. Utilizing an epigenome-wide discovery platform, we elucidate epigenetic alterations in liver tissue from adult offspring (10 months) following perinatal BPA exposure at human physiologically relevant doses (50 ng, 50 μg, and 50 mg BPA/kg diet)...
November 8, 2016: Endocrinology
https://www.readbyqxmd.com/read/27713555/lipid-metabolism-is-associated-with-developmental-epigenetic-programming
#2
Elizabeth H Marchlewicz, Dana C Dolinoy, Lu Tang, Samantha Milewski, Tamara R Jones, Jaclyn M Goodrich, Tanu Soni, Steven E Domino, Peter X K Song, Charles F Burant, Vasantha Padmanabhan
Maternal diet and metabolism impact fetal development. Epigenetic reprogramming facilitates fetal adaptation to these in utero cues. To determine if maternal metabolite levels impact infant DNA methylation globally and at growth and development genes, we followed a clinical birth cohort of 40 mother-infant dyads. Targeted metabolomics and quantitative DNA methylation were analyzed in 1st trimester maternal plasma (M1) and delivery maternal plasma (M2) as well as infant umbilical cord blood plasma (CB). We found very long chain fatty acids, medium chain acylcarnitines, and histidine were: (1) stable in maternal plasma from pregnancy to delivery, (2) significantly correlated between M1, M2, and CB, and (3) in the top 10% of maternal metabolites correlating with infant DNA methylation, suggesting maternal metabolites associated with infant DNA methylation are tightly controlled...
October 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27542345/gene-specific-dna-methylation-may-mediate-atypical-antipsychotic-induced-insulin-resistance
#3
Kyle J Burghardt, Jacyln M Goodrich, Dana C Dolinoy, Vicki L Ellingrod
OBJECTIVES: Atypical antipsychotics (AAPs) carry a significant risk of cardiometabolic side effects, including insulin resistance. It is thought that the insulin resistance resulting from the use of AAPs may be associated with changes in DNA methylation. We aimed to identify and validate a candidate gene associated with AAP-induced insulin resistance by using a multi-step approach that included an epigenome-wide association study (EWAS) and validation with site-specific methylation and metabolomics data...
August 2016: Bipolar Disorders
https://www.readbyqxmd.com/read/27496716/longitudinal-effects-of-developmental-bisphenol-a-and-variable-diet-exposures-on-epigenetic-drift-in-mice
#4
Joseph Kochmanski, Elizabeth H Marchlewicz, Matthew Savidge, Luke Montrose, Christopher Faulk, Dana C Dolinoy
Environmental factors, including exogenous exposures and nutritional status, can affect DNA methylation across the epigenome, but effects of exposures on age-dependent epigenetic drift remain unclear. Here, we tested the hypothesis that early-life exposure to bisphenol A (BPA) and/or variable diet results in altered epigenetic drift, as measured longitudinally via target loci methylation in paired mouse tail tissue (3 wks/10 mos old). Methylation was quantified at two repetitive elements (LINE-1, IAP), two imprinted genes (Igf2, H19), and one non-imprinted gene (Esr1) in isogenic mice developmentally exposed to Control, Control+BPA (50μg/kg diet), Mediterranean, Western, Mediterranean+BPA, or Western+BPA diets...
August 2, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27359112/prenatal-exposures-and-dna-methylation-in-newborns-a-pilot-study-in-durban-south-africa
#5
Jaclyn M Goodrich, Poovendhree Reddy, Rajen N Naidoo, Kareshma Asharam, Stuart Batterman, Dana C Dolinoy
The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive...
July 13, 2016: Environmental Science. Processes & Impacts
https://www.readbyqxmd.com/read/27358748/bisphenol-a-associated-alterations-in-genome-wide-dna-methylation-and-gene-expression-patterns-reveal-sequence-dependent-and-non-monotonic-effects-in-human-fetal-liver
#6
Christopher Faulk, Jung H Kim, Tamara R Jones, Richard C McEachin, Muna S Nahar, Dana C Dolinoy, Maureen A Sartor
Bisphenol A (BPA), a high production volume chemical widely used in consumer products, is an endocrine active compound associated with complex epigenetic responses in animal models and humans. Developmental BPA exposure in mice previously revealed widespread changes in the mouse liver methylome. Here, we undertake the first epigenome-wide analysis of the effect of BPA concentration on human fetal liver DNA methylation. Enzymatic enrichment of genomic DNA for high CG density and methylation followed by next-generation sequencing yielded data for positional methylation across the genome...
December 2015: Environmental Epigenetics
https://www.readbyqxmd.com/read/27334623/epigenome-wide-dna-methylation-analysis-implicates-neuronal-and-inflammatory-signaling-pathways-in-adult-murine-hepatic-tumorigenesis-following-perinatal-exposure-to-bisphenol-a
#7
Caren Weinhouse, Maureen A Sartor, Christopher Faulk, Olivia S Anderson, Karilyn E Sant, Craig Harris, Dana C Dolinoy
Developmental exposure to the endocrine-active compound bisphenol A (BPA) has been linked to epigenotoxic and potential carcinogenic effects in rodent liver, prostate, and mammary glands. A dose-dependent increase in hepatic tumors in 10-month mice perinatally exposed to one of three doses of BPA (50 ng, 50 µg, or 50 mg BPA/kg chow) was previously reported. These tumors represent early-onset disease and lack classical sexual dimorphism in incidence. Here, adult epigenome-wide liver DNA methylation profiles to identify gene promoters associated with perinatal BPA exposure and disease in 10-month mice with and without liver tumors were investigated...
July 2016: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/27267941/detection-of-differential-dna-methylation-in-repetitive-dna-of-mice-and-humans-perinatally-exposed-to-bisphenol-a
#8
Christopher Faulk, Jung H Kim, Olivia S Anderson, Muna S Nahar, Tamara R Jones, Maureen A Sartor, Dana C Dolinoy
Developmental exposure to bisphenol A (BPA) has been shown to induce changes in DNA methylation in both mouse and human genic regions; however, the response in repetitive elements and transposons has not been explored. Here we present novel methodology to combine genomic DNA enrichment with RepeatMasker analysis on next-generation sequencing data to determine the effect of perinatal BPA exposure on repetitive DNA at the class, family, subfamily, and individual insertion level in both mouse and human samples...
July 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27167697/mono-2-ethylhexyl-phthalate-disrupts-neurulation-and-modifies-the-embryonic-redox-environment-and-gene-expression
#9
Karilyn E Sant, Dana C Dolinoy, Joseph L Jilek, Maureen A Sartor, Craig Harris
Mono-2-ethylhexl phthalate (MEHP) is the primary metabolite of di-2-ethylhexyl phthalate (DEHP), a ubiquitous contaminant in plastics. This study sought to determine how structural defects caused by MEHP in mouse whole embryo culture were related to temporal and spatial patterns of redox state and gene expression. MEHP reduced morphology scores along with increased incidence of neural tube defects. Glutathione (GSH) and cysteine (Cys) concentrations fluctuated spatially and temporally in embryo (EMB) and visceral yolk sac (VYS) across the 24h culture...
August 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/26962054/perinatal-lead-exposure-alters-gut-microbiota-composition-and-results-in-sex-specific-bodyweight-increases-in-adult-mice
#10
Jianfeng Wu, Xiaoquan William Wen, Christopher Faulk, Kevin Boehnke, Huapeng Zhang, Dana C Dolinoy, Chuanwu Xi
Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in A(vy) strain wild-type non-agouti (a/a) offspring was tracked through adulthood...
June 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/26851240/correlation-between-conjugated-bisphenol-a-concentrations-and-efflux-transporter-expression-in-human-fetal-livers
#11
Jamie E Moscovitz, Muna S Nahar, Stuart L Shalat, Angela L Slitt, Dana C Dolinoy, Lauren M Aleksunes
Because of its widespread use in the manufacturing of consumer products over several decades, human exposure to bisphenol A (BPA) has been pervasive. Fetuses are particularly sensitive to BPA exposure, with a number of negative developmental and reproductive outcomes observed in rodent perinatal models. Xenobiotic transporters are one mechanism to extrude conjugated and unconjugated BPA from the liver. In this study, the mRNA expression of xenobiotic transporters and relationships with total, conjugated, and free BPA levels were explored utilizing human fetal liver samples...
July 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/26673400/genetic-polymorphisms-are-associated-with-hair-blood-and-urine-mercury-levels-in-the-american-dental-association-ada-study-participants
#12
Rajendra Prasad Parajuli, Jaclyn M Goodrich, Hwai-Nan Chou, Stephen E Gruninger, Dana C Dolinoy, Alfred Franzblau, Niladri Basu
BACKGROUND/AIMS: Mercury (Hg) is a potent toxicant of concern to the general public. Recent studies suggest that several genes that mediate Hg metabolism are polymorphic. We hypothesize that single nucleotide polymorphisms (SNPs) in such genes may underline inter-individual differences in exposure biomarker concentrations. METHODS: Dental professionals were recruited during the American Dental Association (ADA) 2012 Annual Meeting. Samples of hair, blood, and urine were collected for quantifying Hg levels and genotyping (88 SNPs in classes relevant to Hg toxicokinetics including glutathione metabolism, selenoproteins, metallothioneins, and xenobiotic transporters)...
August 2016: Environmental Research
https://www.readbyqxmd.com/read/26542749/stat3-is-a-candidate-epigenetic-biomarker-of-perinatal-bisphenol-a-exposure-associated-with-murine-hepatic-tumors-with-implications-for-human-health
#13
Caren Weinhouse, Ingrid L Bergin, Craig Harris, Dana C Dolinoy
Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that has been implicated as a potential carcinogen and epigenotoxicant. We have previously reported dose-dependent incidence of hepatic tumors in 10-month-old isogenic mice perinatally exposed to BPA. Here, we evaluated DNA methylation at 3 candidate genes (Esr1, Il-6st, and Stat3) in liver tissue of BPA-exposed mice euthanized at 2 time points: post-natal day 22 (PND22; n = 147) or 10-months of age (n = 78, including n = 18 with hepatic tumors). Additionally, DNA methylation profiles were analyzed at human homologs of murine candidate genes in human fetal liver samples (n = 50) with known liver tissue BPA levels...
2015: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/26507544/mono-2-ethylhexyl-phthalate-mehp-alters-histiotrophic-nutrition-pathways-and-epigenetic-processes-in-the-developing-conceptus
#14
Karilyn E Sant, Dana C Dolinoy, Joseph L Jilek, Brian J Shay, Craig Harris
Histiotrophic nutrition pathways (HNPs) are processes by which the organogenesis-stage conceptus obtains nutrients, amino acids, vitamins and cofactors required for protein biosynthesis and metabolic activities. Nutrients are captured from the maternal milieu as whole proteins and cargoes via receptor-mediated endocytosis in the visceral yolk sac (VYS), degraded by lysosomal proteolysis and delivered to the developing embryo (EMB). Several nutrients obtained by HNPs are required substrates for one-carbon (C1) metabolism and supply methyl groups required for epigenetic processes, including DNA and histone methylation...
January 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/26077424/dna-methylation-insulin-resistance-and-second-generation-antipsychotics-in-bipolar-disorder
#15
Kyle J Burghardt, Jacyln M Goodrich, Dana C Dolinoy, Vicki L Ellingrod
AIMS: This study aimed to assess the effect of second-generation antipsychotic (SGA) use and insulin resistance on a global measure of DNA methylation in patients diagnosed with bipolar disorder. MATERIALS & METHODS: Subjects stable on medication (either mood stabilizer monotherapy or adjuvant SGAs) were assessed for insulin resistance. Global methylation levels were assessed in leukocyte DNA from whole blood using the Luminometric Methylation Assay. Multivariable linear regression was used to investigate the effect of insulin resistance and SGA use on DNA methylation...
2015: Epigenomics
https://www.readbyqxmd.com/read/25603046/impact-of-gestational-bisphenol-a-on-oxidative-stress-and-free-fatty-acids-human-association-and-interspecies-animal-testing-studies
#16
Almudena Veiga-Lopez, Subramaniam Pennathur, Kurunthachalam Kannan, Heather B Patisaul, Dana C Dolinoy, Lixia Zeng, Vasantha Padmanabhan
Bisphenol A (BPA) is a high production volume chemical and an endocrine disruptor. Developmental exposures to BPA have been linked to adult metabolic pathologies, but the pathways through which these disruptions occur remain unknown. This is a comprehensive interspecies association vs causal study to evaluate risks posed by prenatal BPA exposure and to facilitate discovery of biomarkers of relevance to BPA toxicity. Samples from human pregnancies during the first trimester and at term, as well as fetal and/or adult samples from prenatally BPA-treated sheep, rats, and mice, were collected to assess the impact of BPA on free fatty acid and oxidative stress dynamics...
March 2015: Endocrinology
https://www.readbyqxmd.com/read/25580720/quality-control-and-statistical-modeling-for-environmental-epigenetics-a-study-on-in-utero-lead-exposure-and-dna-methylation-at-birth
#17
Jaclyn M Goodrich, Brisa N Sánchez, Dana C Dolinoy, Zhenzhen Zhang, Mauricio Hernández-Ávila, Howard Hu, Karen E Peterson, Martha M Téllez-Rojo
DNA methylation data assayed using pyrosequencing techniques are increasingly being used in human cohort studies to investigate associations between epigenetic modifications at candidate genes and exposures to environmental toxicants and to examine environmentally-induced epigenetic alterations as a mechanism underlying observed toxicant-health outcome associations. For instance, in utero lead (Pb) exposure is a neurodevelopmental toxicant of global concern that has also been linked to altered growth in human epidemiological cohorts; a potential mechanism of this association is through alteration of DNA methylation (e...
2015: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/25434263/in-utero-bisphenol-a-concentration-metabolism-and-global-dna-methylation-across-matched-placenta-kidney-and-liver-in-the-human-fetus
#18
Muna S Nahar, Chunyang Liao, Kurunthachalam Kannan, Craig Harris, Dana C Dolinoy
While urine has been an easily accessible and feasible matrix for human biomonitoring, analytical measurements in internal tissues and organs can provide more accurate exposure assessments to understand disease etiology. This is especially important for the endocrine active compound, bisphenol A (BPA), where studies investigating internal doses at sensitive periods of human development are currently lacking. Herein, BPA concentrations, BPA-specific metabolizing enzyme gene expression, and global DNA methylation were characterized across three matched tissues from elective pregnancy terminations of 2nd trimester human fetuses: the placenta, liver, and kidney (N=12 each; N=36 total)...
April 2015: Chemosphere
https://www.readbyqxmd.com/read/25184533/emerging-issues-in-public-health-genomics
#19
REVIEW
J Scott Roberts, Dana C Dolinoy, Beth A Tarini
This review highlights emerging areas of interest in public health genomics. First, we describe recent advances in newborn screening (NBS), with a focus on the practice and policy implications of current and future efforts to expand NBS programs (e.g., via next-generation sequencing). Next, we detail research findings from the rapidly progressing field of epigenetics and epigenomics, highlighting ways in which our emerging understanding in these areas could guide future intervention and research efforts in public health...
2014: Annual Review of Genomics and Human Genetics
https://www.readbyqxmd.com/read/25105421/perinatal-lead-pb-exposure-results-in-sex-specific-effects-on-food-intake-fat-weight-and-insulin-response-across-the-murine-life-course
#20
Christopher Faulk, Amanda Barks, Brisa N Sánchez, Zhenzhen Zhang, Olivia S Anderson, Karen E Peterson, Dana C Dolinoy
Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance...
2014: PloS One
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