1   518 163 ASSOCIATIONS BETWEEN ANTIBIOTIC EXPOSURE DURING PREGNANCY, BIRTH WEIGHT AND ABERRANT METHYLATION AT IMPRINTED GENES AMONG OFFSPRING. OBJECTIVES: LOW BIRTH WEIGHT (LBW) HAS BEEN ASSOCIATED WITH COMMON ADULT-ONSET CHRONIC DISEASES, INCLUDING OBESITY, CARDIOVASCULAR DISEASE, TYPE II DIABETES AND SOME CANCERS. THE ETIOLOGY OF LBW IS MULTI-FACTORIAL. HOWEVER, RECENT EVIDENCE SUGGESTS EXPOSURE TO ANTIBIOTICS MAY ALSO INCREASE THE RISK OF LBW. THE MECHANISMS UNDERLYING THIS ASSOCIATION ARE UNKNOWN, ALTHOUGH EPIGENETIC MECHANISMS ARE HYPOTHESIZED. IN THIS STUDY, WE EVALUATED THE ASSOCIATION BETWEEN MATERNAL ANTIBIOTIC USE AND LBW AND EXAMINED THE POTENTIAL ROLE OF ALTERED DNA METHYLATION THAT CONTROLS GROWTH REGULATORY IMPRINTED GENES IN THESE ASSOCIATIONS. METHODS: BETWEEN 2009-2011, 397 PREGNANT WOMEN WERE ENROLLED AND FOLLOWED UNTIL DELIVERY. PRENATAL ANTIBIOTIC USE WAS ASCERTAINED THROUGH MATERNAL SELF-REPORT. IMPRINTED GENES METHYLATION LEVELS WERE MEASURED AT DIFFERENTIALLY METHYLATED REGIONS (DMRS) USING BISULFITE PYROSEQUENCING. GENERALIZED LINEAR MODELS WERE USED TO EXAMINE ASSOCIATIONS AMONG ANTIBIOTIC USE, BIRTH WEIGHT AND DMR METHYLATION FRACTIONS. RESULTS: AFTER ADJUSTING FOR INFANT GENDER, RACE/ETHNICITY, MATERNAL BODY MASS INDEX, DELIVERY ROUTE, GESTATIONAL WEIGHT GAIN, GESTATIONAL AGE AT DELIVERY, FOLIC ACID INTAKE, PHYSICAL ACTIVITY, MATERNAL SMOKING AND PARITY, ANTIBIOTIC USE DURING PREGNANCY WAS ASSOCIATED WITH 138 G LOWER BIRTH WEIGHT COMPARED WITH NON-ANTIBIOTIC USE (BETA-COEFFICIENT=-132.99, S.E.=50.70, P=0.008). THESE ASSOCIATIONS WERE STRONGEST IN NEWBORNS OF WOMEN WHO REPORTED ANTIBIOTIC USE OTHER THAN PENICILLINS (BETA-COEFFICIENT=-135.57, S.E.=57.38, P=0.02). METHYLATION AT FIVE DMRS, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) AND PEG3 (P=0.08), WAS ASSOCIATED WITH MATERNAL ANTIBIOTIC USE; AMONG THESE, ONLY METHYLATION AT THE PLAGL1 DMR WAS ALSO ASSOCIATED WITH BIRTH WEIGHT. CONCLUSION: WE REPORT AN INVERSE ASSOCIATION BETWEEN IN UTERO EXPOSURE TO ANTIBIOTICS AND LOWER INFANT BIRTH WEIGHT AND PROVIDE THE FIRST EMPIRICAL EVIDENCE SUPPORTING IMPRINTED GENE PLASTICITY IN THESE ASSOCIATIONS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
2  4691  66 NEWBORNS OF OBESE PARENTS HAVE ALTERED DNA METHYLATION PATTERNS AT IMPRINTED GENES. BACKGROUND: SEVERAL EPIDEMIOLOGIC STUDIES HAVE DEMONSTRATED ASSOCIATIONS BETWEEN PERICONCEPTIONAL ENVIRONMENTAL EXPOSURES AND HEALTH STATUS OF THE OFFSPRING IN LATER LIFE. ALTHOUGH THESE ENVIRONMENTALLY RELATED EFFECTS HAVE BEEN ATTRIBUTED TO EPIGENETIC CHANGES, SUCH AS DNA METHYLATION SHIFTS AT IMPRINTED GENES, LITTLE IS KNOWN ABOUT THE POTENTIAL EFFECTS OF MATERNAL AND PATERNAL PRECONCEPTIONAL OVERNUTRITION OR OBESITY. OBJECTIVE: WE EXAMINED PARENTAL PRECONCEPTIONAL OBESITY IN RELATION TO DNA METHYLATION PROFILES AT MULTIPLE HUMAN IMPRINTED GENES IMPORTANT IN NORMAL GROWTH AND DEVELOPMENT, SUCH AS: MATERNALLY EXPRESSED GENE 3 (MEG3), MESODERM-SPECIFIC TRANSCRIPT (MEST), PATERNALLY EXPRESSED GENE 3 (PEG3), PLEIOMORPHIC ADENOMA GENE-LIKE 1 (PLAGL1), EPSILON SARCOGLYCAN AND PATERNALLY EXPRESSED GENE 10 (SGCE/PEG10) AND NEURONATIN (NNAT). METHODS: WE MEASURED METHYLATION PERCENTAGES AT THE DIFFERENTIALLY METHYLATED REGIONS (DMRS) BY BISULFITE PYROSEQUENCING IN DNA EXTRACTED FROM UMBILICAL CORD BLOOD LEUKOCYTES OF 92 NEWBORNS. PRECONCEPTIONAL OBESITY, DEFINED AS BMI ?30 KG M(-2), WAS ASCERTAINED THROUGH STANDARDIZED QUESTIONNAIRES. RESULTS: AFTER ADJUSTING FOR POTENTIAL CONFOUNDERS AND CLUSTER EFFECTS, PATERNAL OBESITY WAS SIGNIFICANTLY ASSOCIATED WITH LOWER METHYLATION LEVELS AT THE MEST (BETA=-2.57; S.E.=0.95; P=0.008), PEG3 (BETA=-1.71; S.E.=0.61; P=0.005) AND NNAT (BETA=-3.59; S.E.=1.76; P=0.04) DMRS. CHANGES RELATED TO MATERNAL OBESITY DETECTED AT OTHER LOCI WERE AS FOLLOWS: BETA-COEFFICIENT WAS +2.58 (S.E.=1.00; P=0.01) AT THE PLAGL1 DMR AND -3.42 (S.E.=1.69; P=0.04) AT THE MEG3 DMR. CONCLUSION: WE FOUND ALTERED METHYLATION OUTCOMES AT MULTIPLE IMPRINT REGULATORY REGIONS IN CHILDREN BORN TO OBESE PARENTS, COMPARED WITH CHILDREN BORN TO NON-OBESE PARENTS. IN SPITE OF THE SMALL SAMPLE SIZE, OUR DATA SUGGEST A PRECONCEPTIONAL INFLUENCE OF PARENTAL LIFE-STYLE OR OVERNUTRITION ON THE (RE)PROGRAMMING OF IMPRINT MARKS DURING GAMETOGENESIS AND EARLY DEVELOPMENT. MORE SPECIFICALLY, THE SIGNIFICANT AND INDEPENDENT ASSOCIATION BETWEEN PATERNAL OBESITY AND THE OFFSPRING'S METHYLATION STATUS SUGGESTS THE SUSCEPTIBILITY OF THE DEVELOPING SPERM FOR ENVIRONMENTAL INSULTS. THE ACQUIRED IMPRINT INSTABILITY MAY BE CARRIED ONTO THE NEXT GENERATION AND INCREASE THE RISK FOR CHRONIC DISEASES IN ADULTHOOD.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
3  2351  67 EPIGENETIC REGULATION OF NEWBORNS' IMPRINTED GENES RELATED TO GESTATIONAL GROWTH: PATTERNING BY PARENTAL RACE/ETHNICITY AND MATERNAL SOCIOECONOMIC STATUS. BACKGROUND: CHILDREN BORN TO PARENTS WITH LOWER INCOME AND EDUCATION ARE AT RISK FOR OBESITY AND LATER-LIFE RISK OF COMMON CHRONIC DISEASES, AND EPIGENETICS HAS BEEN HYPOTHESISED TO LINK THESE ASSOCIATIONS. HOWEVER, EPIGENETIC TARGETS ARE UNKNOWN. WE FOCUS ON A CLUSTER OF WELL-CHARACTERISED GENOMICALLY IMPRINTED GENES BECAUSE THEIR MONOALLELIC EXPRESSION IS REGULATED BY DNA METHYLATION AT DIFFERENTIALLY METHYLATED REGIONS (DMRS), ARE CRITICAL IN FETAL GROWTH, AND DNA METHYLATION PATTERNS AT BIRTH HAVE BEEN ASSOCIATED WITH INCREASED RISK OF BIRTH WEIGHT EXTREMES AND OVERWEIGHT STATUS OR OBESITY IN EARLY CHILDHOOD. METHODS: WE MEASURED DNA METHYLATION AT DMRS REGULATING GENOMICALLY IMPRINTED DOMAINS (IGF2/H19, DLK1/MEG3, NNAT AND PLAGL1) USING UMBILICAL CORD BLOOD LEUCOCYTES FROM 619 INFANTS RECRUITED IN DURHAM, NORTH CAROLINA IN 2010-2011. WE EXAMINED DIFFERENCES IN DNA METHYLATION LEVELS BY RACE/ETHNICITY OF BOTH PARENTS, AND THE ROLE THAT MATERNAL SOCIOECONOMIC STATUS (SES) MAY PLAY IN THE ASSOCIATION BETWEEN RACE/ETHNIC EPIGENETIC DIFFERENCES. RESULTS: UNADJUSTED RACE/ETHNIC DIFFERENCES ONLY WERE EVIDENT FOR DMRS REGULATING MEG3 AND IGF2; RACE/ETHNIC DIFFERENCES PERSISTED IN IGF2/H19 AND NNAT AFTER ACCOUNTING FOR INCOME AND EDUCATION. CONCLUSIONS: RESULTS SUGGEST THAT PARENTAL FACTORS MAY NOT ONLY INFLUENCE DNA METHYLATION, BUT ALSO DO SO IN WAYS THAT VARY BY DMR. FINDINGS SUPPORT THE HYPOTHESIS THAT EPIGENETICS MAY LINK THE OBSERVED LOWER SES DURING THE PRENATAL PERIOD AND POOR OUTCOMES SUCH AS LOW BIRTH WEIGHT; LOWER BIRTH WEIGHT HAS PREVIOUSLY BEEN ASSOCIATED WITH ADULT-ONSET CHRONIC DISEASES AND CONDITIONS THAT INCLUDE CARDIOVASCULAR DISEASES, DIABETES, OBESITY AND SOME CANCERS.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
4   520  44 ASSOCIATIONS BETWEEN MATERNAL PRENATAL STRESS, METHYLATION CHANGES IN IGF1 AND IGF2, AND BIRTH WEIGHT. MATERNAL STRESS HAS BEEN LINKED TO LOW BIRTH WEIGHT IN NEWBORNS. ONE POTENTIAL PATHWAY INVOLVES EPIGENETIC CHANGES AT CANDIDATE GENES THAT MAY MEDIATE THE EFFECTS OF PRENATAL MATERNAL STRESS ON BIRTH WEIGHT. THIS RELATIONSHIP HAS BEEN DOCUMENTED IN STRESS-RELATED GENES, SUCH AS NR3C1. THERE IS LESS LITERATURE EXPLORING THE EFFECT OF STRESS ON GROWTH-RELATED GENES. IGF1 AND IGF2 HAVE BEEN IMPLICATED IN FETAL GROWTH AND DEVELOPMENT, THOUGH VIA DIFFERENT MECHANISMS AS IGF2 IS UNDER IMPRINTING CONTROL. IN THIS STUDY, WE TESTED FOR ASSOCIATIONS BETWEEN PRENATAL STRESS, METHYLATION OF IGF1 AND IGF2, AND BIRTH WEIGHT. A TOTAL OF 24 MOTHER-NEWBORN DYADS IN THE DEMOCRATIC REPUBLIC OF CONGO WERE ENROLLED. ETHNOGRAPHIC INTERVIEWS WERE CONDUCTED WITH MOTHERS AT DELIVERY TO GATHER CULTURALLY RELEVANT WAR-RELATED AND CHRONIC STRESSORS. DNA METHYLATION DATA WERE GENERATED FROM MATERNAL VENOUS, CORD BLOOD AND PLACENTAL TISSUE SAMPLES. MULTIVARIATE REGRESSIONS WERE USED TO TEST FOR ASSOCIATIONS BETWEEN STRESS MEASURES, DNA METHYLATION AND BIRTH WEIGHT IN EACH OF THE THREE TISSUE TYPES. WE FOUND AN ASSOCIATION BETWEEN IGF2 METHYLATION IN MATERNAL BLOOD AND BIRTH WEIGHT. PREVIOUS LITERATURE ON THE RELATIONSHIP BETWEEN IGF2 METHYLATION AND BIRTH WEIGHT HAS FOCUSED ON METHYLATION AT KNOWN DIFFERENTIALLY METHYLATED REGIONS IN CORD BLOOD OR PLACENTAL SAMPLES. OUR FINDINGS INDICATE THERE MAY BE LINKS BETWEEN THE MATERNAL EPIGENOME AND LOW BIRTH WEIGHT THAT RELY ON MECHANISMS OUTSIDE KNOWN IMPRINTING PATHWAYS. IT THUS MAY BE IMPORTANT TO CONSIDER THE EFFECT OF MATERNAL EXPOSURES AND EPIGENETIC PROFILES ON BIRTH WEIGHT EVEN IN THE SETTING OF MATERNALLY IMPRINTED GENES SUCH AS IGF2.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
5  1521  55 DNA METHYLATION AT IMPRINT REGULATORY REGIONS IN PRETERM BIRTH AND INFECTION. OBJECTIVE: TO AID IN UNDERSTANDING LONG-TERM HEALTH CONSEQUENCES OF INTRAUTERINE INFECTIONS IN PRETERM BIRTH, WE EVALUATED DNA METHYLATION AT 9 DIFFERENTIALLY METHYLATED REGIONS THAT REGULATE IMPRINTED GENES BY TYPE OF PRETERM BIRTH (SPONTANEOUS PRETERM LABOR, PRETERM PREMATURE RUPTURE OF MEMBRANES, OR MEDICALLY INDICATED [FETAL GROWTH RESTRICTION AND PREECLAMPSIA]) AND INFECTION STATUS (CHORIOAMNIONITIS OR FUNISITIS). STUDY DESIGN: DATA ON TYPE OF PRETERM BIRTH AND INFECTION STATUS WERE ABSTRACTED FROM MEDICAL RECORDS AND STANDARDIZED PATHOLOGY REPORTS IN 73 PRETERM INFANTS ENROLLED IN THE NEWBORN EPIGENETICS STUDY, A PROSPECTIVE COHORT STUDY OF MOTHER-INFANT DYADS IN DURHAM, NC. CORD BLOOD WAS COLLECTED AT BIRTH, AND INFANT DNA METHYLATION LEVELS AT THE H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, AND PLAGL1 DIFFERENTIALLY METHYLATED REGIONS WERE MEASURED USING BISULFITE PYROSEQUENCING. ONE-WAY ANALYSES OF VARIANCE AND LOGISTIC REGRESSION MODELS WERE USED TO COMPARE DNA METHYLATION LEVELS BY TYPE OF PRETERM BIRTH AND INFECTION STATUS. RESULTS: DNA METHYLATION LEVELS DID NOT DIFFER AT ANY OF THE REGIONS (P > .20) BETWEEN INFANTS BORN VIA SPONTANEOUS PRETERM LABOR (AVERAGE N = 29), PRETERM PREMATURE RUPTURE OF MEMBRANES (AVERAGE N = 17), OR MEDICALLY INDICATED PRETERM BIRTH (AVERAGE N = 40). LEVELS WERE SIGNIFICANTLY INCREASED AT PLAGL1 IN INFANTS WITH CHORIOAMNIONITIS (N = 10, 64.4%) COMPARED WITH INFANTS WITHOUT CHORIOAMNIONITIS (N = 63, 57.9%), P < .01. DNA METHYLATION LEVELS WERE ALSO INCREASED AT PLAGL1 FOR INFANTS WITH FUNISITIS (N = 7, 63.3%) COMPARED WITH INFANTS WITHOUT FUNISITIS (N = 66, 58.3%), P < .05. CONCLUSION: DYSREGULATION OF PLAGL1 HAS BEEN ASSOCIATED WITH ABNORMAL DEVELOPMENT AND CANCER. EARLY-LIFE EXPOSURES, INCLUDING INFECTION/INFLAMMATION, MAY AFFECT EPIGENETIC CHANGES THAT INCREASE SUSCEPTIBILITY TO LATER CHRONIC DISEASE.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
6  6089  52 THE EFFECTS OF DEPRESSION AND USE OF ANTIDEPRESSIVE MEDICINES DURING PREGNANCY ON THE METHYLATION STATUS OF THE IGF2 IMPRINTED CONTROL REGIONS IN THE OFFSPRING. IN UTERO EXPOSURES TO ENVIRONMENTAL FACTORS MAY RESULT IN PERSISTENT EPIGENETIC MODIFICATIONS AFFECTING NORMAL DEVELOPMENT AND SUSCEPTIBILITY TO CHRONIC DISEASES IN LATER LIFE. WE EXPLORED THE RELATIONSHIP BETWEEN EXPOSURE OF THE GROWING FETUS TO MATERNAL DEPRESSION OR ANTIDEPRESSANTS AND DNA METHYLATION AT TWO DIFFERENTIALLY METHYLATED REGIONS (DMRS) OF THE IMPRINTED INSULIN-LIKE GROWTH FACTOR 2 (IGF2) GENE. ABERRANT DNA METHYLATION AT THE IGF2 AND NEIGHBORING H19 DMRS HAS BEEN ASSOCIATED WITH DEREGULATED IGF2 EXPRESSION, CHILDHOOD CANCERS AND SEVERAL CHRONIC DISEASES DURING ADULTHOOD. OUR STUDY POPULATION IS COMPRISED OF PREGNANT MOTHERS AND THEIR NEWBORNS (N = 436), AS PART OF THE NEWBORN EPIGENETICS STUDY (NEST). A STANDARDIZED QUESTIONNAIRE WAS COMPLETED AND MEDICAL RECORD DATA WERE ABSTRACTED TO ASCERTAIN MATERNAL DEPRESSION AND ANTIDEPRESSIVE DRUG USE. DMR METHYLATION LEVELS IN UMBILICAL CORD BLOOD LEUKOCYTES WERE QUANTIFIED USING PYROSEQUENCING. FROM THE 436 NEWBORNS, LABORATORY DATA WERE OBTAINED FOR 356 INDIVIDUALS AT THE IGF2 DMRS, AND FOR 411 INDIVIDUALS AT THE H19 DMRS; ABOUT HALF OF EACH GROUP WAS AFRICAN AMERICAN OR CAUCASIAN. WHILE OVERALL NO ASSOCIATION BETWEEN DEPRESSION AND METHYLATION PROFILES WAS FOUND, WE OBSERVED A SIGNIFICANT HYPERMETHYLATION OF THE H19 DMRS IN NEWBORNS OF AFRICAN AMERICAN (N = 177) BUT NOT CAUCASIAN (N = 168) MOTHERS WHO REPORTED THE USE OF ANTIDEPRESSIVE DRUGS DURING PREGNANCY (BETA = +6.89, P = 0.01). OF NOTE, OUR DATA REVEAL A RACE-INDEPENDENT ASSOCIATION BETWEEN SMOKING DURING PREGNANCY AND METHYLATION AT THE IGF2 DMR (+3.05%, P = 0.01). IN CONCLUSION, OUR FINDINGS SUGGEST A RACE-DEPENDENT RESPONSE RELATED TO MATERNAL USE OF ANTIDEPRESSANTS AT ONE OF THE IGF2 DMRS IN THE OFFSPRING.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
7  5200  35 PRENATAL MATERNAL STRESS PREDICTS METHYLATION OF GENES REGULATING THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL SYSTEM IN MOTHERS AND NEWBORNS IN THE DEMOCRATIC REPUBLIC OF CONGO. EXPOSURE TO STRESS EARLY IN LIFE PERMANENTLY SHAPES ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL (HPA) AXIS AND THE BRAIN. PRENATALLY, GLUCOCORTICOIDS PASS THROUGH THE PLACENTA TO THE FETUS WITH POSTNATAL IMPACTS ON BRAIN DEVELOPMENT, BIRTH WEIGHT (BW), AND HPA AXIS FUNCTIONING. LITTLE IS KNOWN ABOUT THE BIOLOGICAL MECHANISMS BY WHICH PRENATAL STRESS AFFECTS POSTNATAL FUNCTIONING. THIS STUDY ADDRESSES THIS GAP BY EXAMINING THE EFFECT OF CHRONIC STRESS AND TRAUMATIC WAR-RELATED STRESS ON EPIGENETIC CHANGES IN FOUR KEY GENES REGULATING THE HPA AXIS IN NEONATAL CORD BLOOD, PLACENTA, AND MATERNAL BLOOD: CRH, CRHBP, NR3C1, AND FKBP5. PARTICIPANTS WERE 24 MOTHER-NEWBORN DYADS IN THE CONFLICT-RIDDEN REGION OF THE EASTERN DEMOCRATIC REPUBLIC OF CONGO. BW DATA WERE COLLECTED AT DELIVERY AND MATERNAL INTERVIEWS WERE CONDUCTED TO ASSESS CULTURALLY RELEVANT CHRONIC AND WAR-RELATED STRESSORS. CHRONIC STRESS AND WAR TRAUMA HAD WIDESPREAD EFFECTS ON HPA AXIS GENE METHYLATION, WITH SIGNIFICANT EFFECTS OBSERVED AT TRANSCRIPTION FACTOR BINDING (TFB) SITES IN ALL TARGET GENES TESTED. SOME CHANGES IN METHYLATION WERE UNIQUE TO CHRONIC OR WAR STRESS, WHEREAS OTHERS WERE OBSERVED ACROSS BOTH STRESSOR TYPES. MOREOVER, STRESS EXPOSURES IMPACTED MATERNAL AND FETAL TISSUES DIFFERENTLY, SUPPORTING THEORETICAL MODELS THAT STRESS IMPACTS VARY ACCORDING TO LIFE PHASE. METHYLATION IN SEVERAL NR3C1 AND CRH CPG SITES, ALL LOCATED AT TFB SITES, WAS ASSOCIATED WITH BW. THESE FINDINGS SUGGEST THAT PRENATAL STRESS EXPOSURE IMPACTS DEVELOPMENT VIA EPIGENETIC CHANGES IN HPA AXIS GENES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
8   649  53 BIRTHWEIGHT, MATERNAL WEIGHT TRAJECTORIES AND GLOBAL DNA METHYLATION OF LINE-1 REPETITIVE ELEMENTS. LOW BIRTHWEIGHT, PREMATURE BIRTH, INTRAUTERINE GROWTH RETARDATION, AND MATERNAL MALNUTRITION HAVE BEEN RELATED TO AN INCREASED RISK OF CARDIOVASCULAR DISEASE, TYPE 2 DIABETES MELLITUS, OBESITY, AND NEUROPSYCHIATRIC DISORDERS LATER IN LIFE. CONVERSELY, HIGH BIRTHWEIGHT HAS BEEN LINKED TO FUTURE RISK OF CANCER. GLOBAL DNA METHYLATION ESTIMATED BY THE METHYLATION OF REPETITIVE SEQUENCES IN THE GENOME IS AN INDICATOR OF SUSCEPTIBILITY TO CHRONIC DISEASES. WE USED DATA AND BIOSPECIMENS FROM AN EPIGENETIC BIRTH COHORT TO EXPLORE THE ASSOCIATION BETWEEN TRAJECTORIES OF FETAL AND MATERNAL WEIGHT AND LINE-1 METHYLATION IN 319 MOTHER-CHILD DYADS. NEWBORNS WITH LOW OR HIGH BIRTHWEIGHT HAD SIGNIFICANTLY LOWER LINE-1 METHYLATION LEVELS IN THEIR CORD BLOOD COMPARED TO NORMAL WEIGHT INFANTS AFTER ADJUSTING FOR GESTATIONAL AGE, SEX OF THE CHILD, MATERNAL AGE AT DELIVERY, AND MATERNAL SMOKING DURING PREGNANCY (P = 0.007 AND P = 0.036, RESPECTIVELY), BUT THE MAGNITUDE OF THE DIFFERENCE WAS SMALL. INFANTS BORN PREMATURELY ALSO HAD LOWER LINE-1 METHYLATION LEVELS IN CORD BLOOD COMPARED TO TERM INFANTS, AND THIS DIFFERENCE, THOUGH SMALL, WAS STATISTICALLY SIGNIFICANT (P = 0.004). WE DID NOT FIND IMPORTANT ASSOCIATIONS BETWEEN MATERNAL PREPREGNANCY BMI OR GESTATIONAL WEIGHT GAIN AND GLOBAL METHYLATION OF THE CORD BLOOD OR FETAL PLACENTAL TISSUE. IN CONCLUSION, WE FOUND SIGNIFICANT DIFFERENCES IN CORD BLOOD LINE-1 METHYLATION AMONG NEWBORNS WITH LOW AND HIGH BIRTHWEIGHT AS WELL AS AMONG PREMATURELY BORN INFANTS. FUTURE STUDIES MAY ELUCIDATE WHETHER CHROMOSOMAL INSTABILITIES OR OTHER FUNCTIONAL CONSEQUENCES OF THESE CHANGES CONTRIBUTE TO THE INCREASED RISK OF CHRONIC DISEASES AMONG INDIVIDUALS WITH THESE CHARACTERISTICS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
9  4066  49 MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION AS AN INDICATOR OF OFFSPRING METABOLIC SYNDROME RISK IN LATER LIFE THROUGH EPIGENETIC IMPRINTING: A SYSTEMATIC REVIEW. AIMS: THIS REVIEW EXAMINED WHETHER MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION EFFECTS AN OFFSPRING'S LIKELIHOOD OF DEVELOPING CHRONIC METABOLIC RELATED CONDITIONS DUE TO EPIGENETIC IMPRINTING. METHODS: A LITERATURE SEARCH WAS CONDUCTED IN MULTIPLE SCIENCE DATABASES AND LIMITED TO STUDIES PUBLISHED AFTER 2012, IN ENGLISH LANGUAGE AND PEER REVIEWED. THE DATA FROM SELECTED ARTICLES WERE EXTRACTED AND A QUALITATIVE APPROACH WAS EMPLOYED DUE TO HETEROGENEITY OF RESULTS. RESULTS: NEWBORNS FROM OBESE FATHERS SHOWED ALTERED METHYLATION OVERALL AND SIGNIFICANT HYPOMETHYLATION AT THE INSULIN-LIKE GROWTH FACTOR 2 (IGF2) GENE. HIGH MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) WAS ASSOCIATED WITH ALTERED OFFSPRING DNA METHYLATION LEVELS AND GESTATIONAL DIABETES MELLITUS INDUCED SIGNIFICANTLY INCREASED METHYLATION LEVELS IN OFFSPRING. GESTATIONAL WEIGHT GAIN WAS NOT ASSOCIATED WITH DIFFERENTIALLY METHYLATED CORD BLOOD. BIRTH WEIGHT WAS HIGHER IN OFFSPRING EXPOSED TO FAMINE IN EARLY GESTATION. OFFSPRING BORN POST MATERNAL BARIATRIC SURGERY SHOWED A LOWER PERCENTAGE OF BODY FAT AND IMPROVED FASTING INSULIN LEVELS COMPARED TO SIBLINGS BORN PRE-MATERNAL BARIATRIC SURGERY. CONCLUSIONS: THE AVAILABLE EVIDENCE SUGGESTS THAT POOR MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION CAN INCREASE THE RISK OF METABOLIC SYNDROME IN OFFSPRING, THROUGH EPIGENETIC IMPRINTING. POTENTIAL PARENTS SHOULD BE ADVISED THAT MAINTAINING A HEALTHY DIET AND BMI IS LIKELY TO REDUCE THE RISK OF METABOLIC SYNDROME IN OFFSPRING.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
10  4010  51 LOW MATERNAL ADHERENCE TO A MEDITERRANEAN DIET IS ASSOCIATED WITH INCREASE IN METHYLATION AT THE MEG3-IG DIFFERENTIALLY METHYLATED REGION IN FEMALE INFANTS. DIET IS DICTATED BY THE SURROUNDING ENVIRONMENT, AS FOOD ACCESS AND AVAILABILITY MAY CHANGE DEPENDING ON WHERE ONE LIVES. MATERNAL DIET DURING PREGNANCY IS AN IMPORTANT PART OF THE IN UTERO ENVIRONMENT, AND MAY AFFECT THE EPIGENOME. STUDIES LOOKING AT OVERALL DIET PATTERN IN RELATION TO DNA METHYLATION HAVE BEEN LACKING. THE MEDITERRANEAN DIET IS KNOWN FOR ITS HEALTH BENEFITS, INCLUDING DECREASED INFLAMMATION, WEIGHT LOSS, AND MANAGEMENT OF CHRONIC DISEASES. THIS STUDY ASSESSES THE ASSOCIATION BETWEEN MATERNAL ADHERENCE TO A MEDITERRANEAN DIET PATTERN DURING PREGNANCY AND INFANT DNA METHYLATION AT BIRTH. MEDITERRANEAN DIET ADHERENCE IN EARLY PREGNANCY WAS MEASURED IN 390 WOMEN ENROLLED IN THE NEWBORN EPIGENETIC STUDY, AND DNA METHYLATION WAS ASSESSED IN THEIR INFANTS AT BIRTH. MULTINOMIAL LOGISTIC REGRESSION WAS USED TO ASSESS THE ASSOCIATION BETWEEN ADHERENCE TO A MEDITERRANEAN DIET AND INFANT METHYLATION AT THE MEG3, MEG3-IG, PLEIOMORPHIC ADENOMA GENE-LIKE 1, INSULIN-LIKE GROWTH FACTOR 2 GENE, H19, MESODERM-SPECIFIC TRANSCRIPT, NEURONATIN, PATERNALLY EXPRESSED GENE 3, SARCOGLYCAN AND PATERNALLY EXPRESSED GENE 10 REGIONS, MEASURED BY PYROSEQUENCING. INFANTS OF MOTHERS WITH A LOW ADHERENCE TO A MEDITERRANEAN DIET HAD A GREATER ODDS OF HYPO-METHYLATION AT THE MEG3-IG DIFFERENTIALLY METHYLATED REGION (DMR). SEX-STRATIFIED MODELS SHOWED THAT THIS ASSOCIATION WAS PRESENT IN GIRLS ONLY. THIS STUDY PROVIDES EARLY EVIDENCE ON THE ASSOCIATION BETWEEN OVERALL DIET PATTERN AND METHYLATION AT THE 9 DMRS INCLUDED IN THIS STUDY, AND SUGGESTS THAT MATERNAL DIET CAN HAVE A SEX-SPECIFIC IMPACT ON INFANT DNA METHYLATION AT SPECIFIC IMPRINTED DMRS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
11  4504  41 MOTHER'S PRE-PREGNANCY BMI AND PLACENTAL CANDIDATE MIRNAS: FINDINGS FROM THE ENVIRONAGE BIRTH COHORT. THERE IS INCREASING EVIDENCE THAT THE PREDISPOSITION FOR DEVELOPMENT OF CHRONIC DISEASES ARISES AT THE EARLIEST TIMES OF LIFE. IN THIS CONTEXT, MATERNAL PRE-PREGNANCY WEIGHT MIGHT MODIFY FETAL METABOLISM AND THE CHILD'S PREDISPOSITION TO DEVELOP DISEASE LATER IN LIFE. THE AIM OF THIS STUDY IS TO INVESTIGATE THE ASSOCIATION BETWEEN MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) AND MIRNA ALTERATIONS IN PLACENTAL TISSUE AT BIRTH. IN 211 MOTHER-NEWBORN PAIRS FROM THE ENVIRONAGE BIRTH COHORT, WE ASSESSED PLACENTAL EXPRESSION OF SEVEN MIRNAS IMPORTANT IN CRUCIAL CELLULAR PROCESSES IMPLICATED IN ADIPOGENESIS AND/OR OBESITY. MULTIPLE LINEAR REGRESSION MODELS WERE USED TO ADDRESS THE ASSOCIATIONS BETWEEN PRE-PREGNANCY BMI AND PLACENTAL CANDIDATE MIRNA EXPRESSION. MATERNAL PRE-PREGNANCY BMI AVERAGED (+/-SD) 23.9 (+/-4.1) KG/M(2). IN NEWBORN GIRLS (NOT IN BOYS) PLACENTAL MIR-20A, MIR-34A AND MIR-222 EXPRESSION WAS LOWER WITH HIGHER MATERNAL PRE-PREGNANCY BMI. IN ADDITION, THE ASSOCIATION BETWEEN MATERNAL PRE-PREGNANCY BMI AND PLACENTAL EXPRESSION OF THESE MIRNAS IN GIRLS WAS MODIFIED BY GESTATIONAL WEIGHT GAIN. THE LOWER EXPRESSION OF THESE MIRNAS IN PLACENTA IN ASSOCIATION WITH PRE-PREGNANCY BMI, WAS ONLY EVIDENT IN MOTHERS WITH LOW WEIGHT GAIN (<14 KG). THE PLACENTAL EXPRESSION OF MIR-20A, MIR-34A, MIR-146A, MIR-210 AND MIR-222 MAY PROVIDE A SEX-SPECIFIC BASIS FOR EPIGENETIC EFFECTS OF PRE-PREGNANCY BMI.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
12  2903  63 GENDER-SPECIFIC METHYLATION DIFFERENCES IN RELATION TO PRENATAL EXPOSURE TO CIGARETTE SMOKE. EPIGENETIC ALTERATIONS MAY MECHANISTICALLY EXPLAIN THE DEVELOPMENTAL ORIGINS OF ADULT DISEASE, NAMELY THE HYPOTHESIS THAT MANY COMPLEX ADULT CHRONIC DISEASES ORIGINATE AS A RESULT OF CONDITIONS ENCOUNTERED IN UTERO. IF TRUE, EPIGENETICALLY REGULATED IMPRINTED GENES, CRITICAL TO NORMAL GROWTH AND DEVELOPMENT, MAY PARTIALLY MEDIATE THESE OUTCOMES. WE DETERMINED THE INFLUENCE OF IN UTERO EXPOSURE TO CIGARETTE SMOKING ON METHYLATION AT TWO DIFFERENTIALLY METHYLATED REGIONS (DMRS) REGULATING INSULIN-LIKE GROWTH FACTOR 2 (IGF2) AND H19, AND HOW THIS MIGHT RELATE TO BIRTH WEIGHT OF INFANTS BORN TO 418 PREGNANT WOMEN. SMOKING STATUS WAS ASCERTAINED THROUGH SELF-REPORT AND MEDICAL RECORDS. BISULFITE PYROSEQUENCING WAS USED TO MEASURE METHYLATION IN UMBILICAL CORD BLOOD DNAS. LEAST SQUARES DNA METHYLATION MEANS AT EACH DMR AND BIRTH WEIGHT WERE COMPARED BETWEEN INFANTS OF SMOKERS AND NON-SMOKERS, USING GENERALIZED LINEAR MODELS. WHILE THERE WERE NO SIGNIFICANT DIFFERENCES AT THE H19 DMR, INFANTS BORN TO SMOKERS HAD HIGHER METHYLATION AT THE IGF2 DMR THAN THOSE BORN TO NEVER SMOKERS OR THOSE WHO QUIT DURING PREGNANCY (49.5%, SD=8.0 VERSUS 46.6%, SD=5.6 AND 45.8%, SD=6.3, RESPECTIVELY; P=0.0002). THE SMOKING-RELATED INCREASE IN METHYLATION WAS MOST PRONOUNCED IN MALE OFFSPRING (P FOR SEX INTERACTION=0.03), FOR WHOM APPROXIMATELY 20% OF SMOKING-RELATED LOW BIRTH WEIGHT WAS MEDIATED BY DNA METHYLATION AT THE IGF2 DMR. OUR FINDINGS SUGGEST THAT IGF2 DMR PLASTICITY IS AN IMPORTANT MECHANISM BY WHICH IN UTERO ADJUSTMENTS TO ENVIRONMENTAL TOXICANTS ARE CONFERRED. LARGER STUDIES TO REPLICATE THESE FINDINGS ARE REQUIRED.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
13   521  46 ASSOCIATIONS BETWEEN MATERNAL PSYCHOSOCIAL STRESS, DNA METHYLATION, AND NEWBORN BIRTH WEIGHT IDENTIFIED BY INVESTIGATING METHYLATION AT INDIVIDUAL, REGIONAL, AND GENOME LEVELS. STRESS IS KNOWN TO AFFECT HEALTH THROUGHOUT LIFE AND INTO FUTURE GENERATIONS, BUT THE UNDERLYING MOLECULAR MECHANISMS ARE UNKNOWN. WE TESTED THE HYPOTHESIS THAT MATERNAL PSYCHOSOCIAL STRESS INFLUENCES DNA METHYLATION (DNAM), WHICH IN TURN IMPACTS NEWBORN HEALTH OUTCOMES. SPECIFICALLY, WE ANALYZED DNAM AT INDIVIDUAL, REGIONAL, AND GENOME-WIDE LEVELS TO TEST FOR ASSOCIATIONS WITH MATERNAL STRESS AND NEWBORN BIRTH WEIGHT. MATERNAL VENOUS BLOOD AND NEWBORN CORD BLOOD (N = 24 AND 22, RESPECTIVELY) WERE ASSAYED FOR METHYLATION AT APPROXIMATELY 450,000 CPG SITES. METHYLATION WAS ANALYZED BY EXAMINING CPG SITES INDIVIDUALLY IN AN EPIGENOME-WIDE ASSOCIATION STUDY (EWAS), AS REGIONAL GROUPS USING VARIABLY METHYLATED REGION (VMR) ANALYSIS IN MATERNAL BLOOD ONLY, AND THROUGH THE EPIGENOME-WIDE MEASURES USING GENOME-WIDE MEAN METHYLATION (GMM), HORVATH'S EPIGENETIC CLOCK, AND MITOTIC AGE. THESE METHYLATION MEASURES WERE TESTED FOR ASSOCIATION WITH THREE MEASURES OF MATERNAL STRESS (MATERNAL WAR TRAUMA, CHRONIC STRESS, AND EXPERIENCE OF SEXUAL VIOLENCE) AND ONE HEALTH OUTCOME (NEWBORN BIRTH WEIGHT). WE OBSERVED THAT MATERNAL EXPERIENCES OF WAR TRAUMA, CHRONIC STRESS, AND SEXUAL ASSAULT WERE EACH ASSOCIATED WITH DECREASED NEWBORN BIRTH WEIGHT (P < 1.95 X 10(-7) IN ALL CASES). TESTING INDIVIDUAL CPG SITES USING EWAS, WE OBSERVED NO ASSOCIATIONS BETWEEN DNAM AND ANY MEASURE OF MATERNAL STRESS OR NEWBORN BIRTH WEIGHT IN EITHER MATERNAL OR CORD BLOOD, AFTER BONFERRONI MULTIPLE TESTING CORRECTION. HOWEVER, THE TOP-RANKED CPG SITE IN MATERNAL BLOOD THAT ASSOCIATED WITH MATERNAL CHRONIC STRESS AND SEXUAL VIOLENCE BEFORE MULTIPLE TESTING CORRECTION IS LOCATED NEAR THE SPON1 GENE. TESTING AT A REGIONAL LEVEL, WE FOUND INCREASED METHYLATION OF A VMR IN MATERNAL BLOOD NEAR SPON1 THAT WAS ASSOCIATED WITH CHRONIC STRESS AND SEXUAL VIOLENCE AFTER BONFERRONI MULTIPLE TESTING CORRECTION (P = 1.95 X 10(-7) AND 8.3 X 10(-6), RESPECTIVELY). AT THE EPIGENOMIC LEVEL, CORD BLOOD GMM WAS ASSOCIATED WITH SIGNIFICANTLY HIGHER LEVELS OF WAR TRAUMA (P = 0.025) AND WAS SUGGESTIVELY ASSOCIATED WITH SEXUAL VIOLENCE (P = 0.053). THE OTHER TWO EPIGENOME-WIDE MEASURES WERE NOT ASSOCIATED WITH MATERNAL STRESS OR NEWBORN BIRTH WEIGHT IN EITHER TISSUE TYPE. DESPITE OUR SMALL SAMPLE SIZE, WE IDENTIFIED ASSOCIATIONS EVEN AFTER CONSERVATIVE MULTIPLE TESTING CORRECTION. SPECIFICALLY, WE FOUND ASSOCIATIONS BETWEEN DNAM AND THE THREE MEASURES OF MATERNAL STRESS ACROSS BOTH TISSUES; SPECIFICALLY, A VMR IN MATERNAL BLOOD AND GMM IN CORD BLOOD WERE BOTH ASSOCIATED WITH DIFFERENT MEASURES OF MATERNAL STRESS. THE ASSOCIATION OF CORD BLOOD GMM, BUT NOT MATERNAL BLOOD GMM, WITH MATERNAL STRESS MAY SUGGEST DIFFERENT RESPONSES TO STRESS IN MOTHER AND NEWBORN. IT IS NOTEWORTHY THAT WE FOUND ASSOCIATIONS ONLY WHEN CPG SITES WERE ANALYZED IN AGGREGATE, EITHER AS VMRS OR AS A BROAD SUMMARY MEASURE OF GMM.	2019	

14  4223  37 METHYLATION CHANGES AT NR3C1 IN NEWBORNS ASSOCIATE WITH MATERNAL PRENATAL STRESS EXPOSURE AND NEWBORN BIRTH WEIGHT. EARLY LIFE EXPERIENCES, INCLUDING THOSE IN UTERO, HAVE BEEN LINKED TO INCREASED RISK FOR ADULT-ONSET CHRONIC DISEASE. THE UNDERLYING ASSUMPTION IS THAT THERE IS A CRITICAL PERIOD OF DEVELOPMENTAL PLASTICITY IN UTERO WHEN SELECTION OF THE FETAL PHENOTYPE THAT IS BEST ADAPTED TO THE INTRAUTERINE ENVIRONMENT OCCURS. THE CURRENT STUDY IS THE FIRST TO TEST THE IDEA THAT EXTREME MATERNAL PSYCHOSOCIAL STRESSORS, AS OBSERVED IN THE DEMOCRATIC REPUBLIC OF CONGO, MAY MODIFY LOCUS-SPECIFIC EPIGENETIC MARKS IN THE NEWBORN RESULTING IN ALTERED HEALTH OUTCOMES. HERE WE SHOW A SIGNIFICANT CORRELATION BETWEEN CULTURALLY RELEVANT MEASURES OF MATERNAL PRENATAL STRESS, NEWBORN BIRTH WEIGHT AND NEWBORN METHYLATION IN THE PROMOTER OF THE GLUCOCORTICOID RECEPTOR NR3C1. INCREASED METHYLATION MAY CONSTRAIN PLASTICITY IN SUBSEQUENT GENE EXPRESSION AND RESTRICT THE RANGE OF STRESS ADAPTATION RESPONSES POSSIBLE IN AFFECTED INDIVIDUALS, THUS INCREASING THEIR RISK FOR ADULT-ONSET DISEASES.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
15  6270  57 THE OBESOGENIC ENVIRONMENT: EPIGENETIC MODIFICATIONS IN PLACENTAL MELANOCORTIN 4 RECEPTOR GENE CONNECTED TO GESTATIONAL DIABETES AND SMOKING. BACKGROUND: MATERNAL METABOLIC INSULTS AS WELL AS GESTATIONAL DIABETES MELLITUS (GDM) INFLUENCE THE FETAL HEALTH AND MAY AFFECT 'OFFSPRING'S SUSCEPTIBILITY TO CHRONIC DISEASES VIA EPIGENETIC MODIFICATIONS. GDM, THE MOST COMMON METABOLIC DISORDER IN PREGNANCY, CAN BE CONSIDERED THE RESULT OF COMPLEX INTERACTIONS BETWEEN GENETIC AND ENVIRONMENTAL FACTORS. A CRITICAL POINT IN THIS VIEW IS THE IDENTIFICATION OF GENES WHICH ARE EPIGENETICALLY MODIFIED UNDER THE INFLUENCE OF GDM. THE MELANOCORTIN 4 RECEPTOR (MC4R) GENE PLAYS A CRUCIAL ROLE IN NUTRITIONAL HEALTH BY SUPPRESSING APPETITE AND PARTICIPATING IN ENERGY CONTROL REGULATION. THE CORRELATIONS BETWEEN PREGNANT 'WOMEN'S METABOLIC PROFILES AND PLACENTAL EPIGENETIC MODIFICATIONS OF THIS GENE HAVE BEEN POORLY INVESTIGATED. OBJECTIVE: THE AIM OF THIS STUDY WAS TO EVALUATE THE EFFECT OF GDM AND MATERNAL CLINICAL PARAMETERS AT THE THIRD TRIMESTER OF PREGNANCY TO DNA METHYLATION LEVELS IN THE PLACENTA AT CPG SITES OF MC4R GENE. DESIGN AND METHODS: SOCIO-DEMOGRAPHIC AND CLINICAL CHARACTERISTICS, MEDITERRANEAN DIET ADHERENCE, SMOKING HABITS, AND PHYSICAL ACTIVITY WERE ASSESSED AT THE THIRD TRIMESTER OF PREGNANCY OF 60 CAUCASIAN PREGNANT WOMEN, OF WHICH 33 WITH GDM. CLINICAL PARAMETERS OF THE NEWBORNS WERE RECORDED AT BIRTH. MC4R DNA METHYLATION ON MATERNAL AND FETAL SIDES OF THE PLACENTA WAS ANALYZED USING BISULFITE PYROSEQUENCING. RESULTS: MC4R DNA METHYLATION LEVELS AT CPG1 AND CPG2 WERE LOWER ON THE FETAL SIDE OF THE PLACENTA IN GDM-AFFECTED WOMEN THAN IN NON-GDM-AFFECTED RECRUITS (P = 0.033). MOREOVER, DNA METHYLATION LEVELS ON THE MATERNAL SIDE AT CPG1 WERE POSITIVELY RELATED TO GLUCOSE CONCENTRATION AT 2-H ORAL GLUCOSE TOLERANCE TEST (OGTT). ON THE OTHER HAND, CPG2 DNA METHYLATION WAS POSITIVELY RELATED TO BOTH 1-H AND 2-H DURING OGTT. MATERNAL DNA METHYLATION LEVEL AT CPG2 WAS ALSO ASSOCIATED WITH LOW DENSITY LIPOPROTEIN CHOLESTEROL (LDL-C) AT THE THIRD TRIMESTER OF PREGNANCY (RHO = 0.340, P < 0.05), WHILE CPG1 METHYLATION WAS NEGATIVELY RELATED TO MATERNAL WEIGHT VARIATIONS AT DELIVERY (RHO = -0.316, P < 0.05). SIGNIFICANT ASSOCIATIONS BETWEEN MC4R DNA METHYLATION ON THE MATERNAL SIDE AND LIPID PROFILE AT THIRD TRIMESTER OF PREGNANCY IN WOMEN SMOKERS WERE FOUND. CONCLUSION: OUR RESULTS SUGGEST THAT MC4R METHYLATION PROFILE IN THE PLACENTA IS RELATED TO MATERNAL METABOLIC AND NUTRITIONAL CONDITIONS, POTENTIALLY AFFECTING FETAL PROGRAMMING AND THE FUTURE METABOLIC HEALTH OF THE NEWBORN.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                
16  5192  44 PRENATAL ENVIRONMENTAL STRESSORS AND DNA METHYLATION LEVELS IN PLACENTA AND PERIPHERAL TISSUES OF MOTHERS AND NEONATES EVALUATED BY APPLYING ARTIFICIAL NEURAL NETWORKS. EXPOSURE TO ENVIRONMENTAL STRESSORS DURING PREGNANCY PLAYS AN IMPORTANT ROLE IN INFLUENCING SUBSEQUENT SUSCEPTIBILITY TO CERTAIN CHRONIC DISEASES THROUGH THE MODULATION OF EPIGENETIC MECHANISMS, INCLUDING DNA METHYLATION. OUR AIM WAS TO EXPLORE THE CONNECTIONS BETWEEN ENVIRONMENTAL EXPOSURES DURING GESTATION WITH DNA METHYLATION OF PLACENTAL CELLS, MATERNAL AND NEONATAL BUCCAL CELLS BY APPLYING ARTIFICIAL NEURAL NETWORKS (ANNS). A TOTAL OF 28 MOTHER-INFANT PAIRS WERE ENROLLED. DATA ON GESTATIONAL EXPOSURE TO ADVERSE ENVIRONMENTAL FACTORS AND ON MOTHER HEALTH STATUS WERE COLLECTED THROUGH THE ADMINISTRATION OF A QUESTIONNAIRE. DNA METHYLATION ANALYSES AT BOTH GENE-SPECIFIC AND GLOBAL LEVEL WERE ANALYZED IN PLACENTAS, MATERNAL AND NEONATAL BUCCAL CELLS. IN THE PLACENTA, THE CONCENTRATIONS OF VARIOUS METALS AND DIOXINS WERE ALSO ANALYZED. ANALYSIS OF ANNS REVEALED THAT SUBOPTIMAL BIRTH WEIGHT IS ASSOCIATED WITH PLACENTAL H19 METHYLATION, MATERNAL STRESS DURING PREGNANCY WITH METHYLATION LEVELS OF NR3C1 AND BDNF IN PLACENTAS AND MOTHER'S BUCCAL DNA, RESPECTIVELY, AND EXPOSURE TO AIR POLLUTANTS WITH MATERNAL MGMT METHYLATION. ASSOCIATIONS WERE ALSO OBSERVED BETWEEN PLACENTAL CONCENTRATIONS OF LEAD, CHROMIUM, CADMIUM AND MERCURY WITH METHYLATION LEVELS OF OXTR IN PLACENTAS, HSD11B2 IN MATERNAL BUCCAL CELLS AND PLACENTAS, MECP2 IN NEONATAL BUCCAL CELLS, AND MTHFR IN MATERNAL BUCCAL CELLS. FURTHERMORE, DIOXIN CONCENTRATIONS WERE ASSOCIATED WITH PLACENTAL RELN, NEONATAL HSD11B2 AND MATERNAL H19 GENE METHYLATION LEVELS. CURRENT RESULTS SUGGEST THAT EXPOSURE OF PREGNANT WOMEN TO ENVIRONMENTAL STRESSORS DURING PREGNANCY COULD INDUCE ABERRANT METHYLATION LEVELS IN GENES LINKED TO SEVERAL PATHWAYS IMPORTANT FOR EMBRYOGENESIS IN BOTH THE PLACENTA, POTENTIALLY AFFECTING FOETAL DEVELOPMENT, AND IN THE PERIPHERAL TISSUES OF MOTHERS AND INFANTS, POTENTIALLY PROVIDING PERIPHERAL BIOMARKERS OF ENVIRONMENTAL EXPOSURE.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
17   668  41 BNDF METHYLATION IN MOTHERS AND NEWBORNS IS ASSOCIATED WITH MATERNAL EXPOSURE TO WAR TRAUMA. BACKGROUND: THE BDNF GENE CODES FOR BRAIN-DERIVED NEUROTROPHIC FACTOR, A GROWTH FACTOR INVOLVED IN NEURAL DEVELOPMENT, CELL DIFFERENTIATION, AND SYNAPTIC PLASTICITY. PRESENT IN BOTH THE BRAIN AND PERIPHERY, BDNF PLAYS CRITICAL ROLES THROUGHOUT THE BODY AND IS ESSENTIAL FOR PLACENTAL AND FETAL DEVELOPMENT. RODENT STUDIES SHOW THAT EARLY LIFE STRESS, INCLUDING PRENATAL STRESS, BROADLY ALTERS BDNF METHYLATION, WITH PRESUMED CHANGES IN GENE EXPRESSION. NO STUDIES HAVE ASSESSED PRENATAL EXPOSURE TO MATERNAL TRAUMATIC STRESS AND BDNF METHYLATION IN HUMANS. THIS STUDY EXAMINED ASSOCIATIONS OF PRENATAL EXPOSURE TO MATERNAL STRESS AND BDNF METHYLATION AT CPG SITES ACROSS THE BDNF GENE. RESULTS: AMONG 24 MOTHERS AND NEWBORNS IN THE EASTERN DEMOCRATIC REPUBLIC OF CONGO, A REGION WITH EXTREME CONFLICT AND VIOLENCE TO WOMEN, MATERNAL EXPERIENCES OF WAR TRAUMA AND CHRONIC STRESS WERE ASSOCIATED WITH BDNF METHYLATION IN UMBILICAL CORD BLOOD, PLACENTAL TISSUE, AND MATERNAL VENOUS BLOOD. ASSOCIATIONS OF MATERNAL STRESS AND BDNF METHYLATION SHOWED HIGH TISSUE SPECIFICITY. THE MAJORITY OF SIGNIFICANT ASSOCIATIONS WERE OBSERVED IN PUTATIVE TRANSCRIPTION FACTOR BINDING REGIONS. CONCLUSIONS: THIS IS THE FIRST STUDY IN HUMANS TO EXAMINE BDNF METHYLATION IN RELATION TO PRENATAL EXPOSURE TO MATERNAL STRESS IN THREE TISSUES SIMULTANEOUSLY AND THE FIRST IN ANY MAMMALIAN SPECIES TO REPORT ASSOCIATIONS OF PRENATAL STRESS AND BDNF METHYLATION IN PLACENTAL TISSUE. THE FINDINGS ADD TO THE GROWING BODY OF EVIDENCE HIGHLIGHTING THE IMPORTANCE OF CONSIDERING EPIGENETIC EFFECTS WHEN EXAMINING THE IMPACTS OF TRAUMA AND STRESS, NOT ONLY FOR ADULTS BUT ALSO FOR OFFSPRING EXPOSED VIA EFFECTS TRANSMITTED BEFORE BIRTH.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
18  5658  37 SEX-DIMORPHIC PATHWAYS IN THE ASSOCIATIONS BETWEEN MATERNAL TRAIT ANXIETY, INFANT BDNF METHYLATION, AND NEGATIVE EMOTIONALITY. MATERNAL ANTENATAL ANXIETY IS AN EMERGING RISK FACTOR FOR CHILD EMOTIONAL DEVELOPMENT. BOTH SEX AND EPIGENETIC MECHANISMS, SUCH AS DNA METHYLATION, MAY CONTRIBUTE TO THE EMBEDDING OF MATERNAL DISTRESS INTO EMOTIONAL OUTCOMES. HERE, WE INVESTIGATED SEX-DEPENDENT PATTERNS IN THE ASSOCIATION BETWEEN ANTENATAL MATERNAL TRAIT ANXIETY, METHYLATION OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR GENE (BDNF DNAM), AND INFANT NEGATIVE EMOTIONALITY (NE). MOTHER-INFANT DYADS (N = 276) WERE RECRUITED AT DELIVERY. MATERNAL TRAIT ANXIETY, AS A MARKER OF ANTENATAL CHRONIC STRESS EXPOSURE, WAS ASSESSED SOON AFTER DELIVERY USING THE STAIT-TRAIT ANXIETY INVENTORY (STAI-Y). INFANTS' BDNF DNAM AT BIRTH WAS ASSESSED IN 11 CPG SITES IN BUCCAL CELLS WHEREAS INFANTS' NE WAS ASSESSED AT 3 (N = 225) AND 6 MONTHS (N = 189) USING THE INFANT BEHAVIOR QUESTIONNAIRE-REVISED (IBQ-R). HIERARCHICAL LINEAR ANALYSES SHOWED THAT HIGHER MATERNAL ANTENATAL ANXIETY WAS ASSOCIATED WITH GREATER 6-MONTH-OLDS' NE. FURTHERMORE, MATERNAL ANTENATAL ANXIETY PREDICTED GREATER INFANTS' BDNF DNAM IN FIVE CPG SITES IN MALES BUT NOT IN FEMALES. HIGHER METHYLATION AT THESE SITES WAS ASSOCIATED WITH GREATER 3-TO-6-MONTH NE INCREASE, INDEPENDENTLY OF INFANTS' SEX. MATERNAL ANTENATAL ANXIETY EMERGED AS A RISK FACTOR FOR INFANT'S NE. BDNF DNAM MIGHT MEDIATE THIS EFFECT IN MALES. THESE RESULTS MAY INFORM THE DEVELOPMENT OF STRATEGIES TO PROMOTE MOTHERS AND INFANTS' EMOTIONAL WELL-BEING.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
19  4065  38 MATERNAL AND GESTATIONAL INFLUENCES ON CHILDHOOD BLOOD PRESSURE. EXPOSURES THAT CONTRIBUTE TO A SUB-OPTIMAL INTRAUTERINE ENVIRONMENT CAN HAVE AN EFFECT ON THE DEVELOPING FETUS. IMPAIRED FETAL GROWTH THAT RESULTS IN LOW BIRTH WEIGHT IS AN ESTABLISHED RISK FACTOR FOR CARDIO-METABOLIC DISORDERS LATER IN LIFE. RECENT EPIDEMIOLOGIC AND PROSPECTIVE COHORT STUDIES THAT INCLUDE THE MATERNAL AND GESTATIONAL PERIOD HAVE IDENTIFIED MATERNAL AND GESTATIONAL CONDITIONS THAT CONFER INCREASED RISK FOR SUBSEQUENT CARDIO-METABOLIC DISORDERS IN THE ABSENCE OF LOW BIRTH WEIGHT. MATERNAL PRE-CONCEPTION HEALTH STATUS, INCLUDING CHRONIC OBESITY AND TYPE 2 DIABETES, INCREASE RISK FOR CHILDHOOD OBESITY AND OBESITY-RELATED HIGHER BLOOD PRESSURE (BP) IN CHILD OFFSPRING. MATERNAL GESTATIONAL EXPOSURES, INCLUDING GESTATIONAL DIABETES, GESTATIONAL HYPERTENSION, AND PREECLAMPSIA, ARE ASSOCIATED WITH HIGHER BP IN OFFSPRING. OTHER MATERNAL EXPOSURES SUCH AS CIGARETTE SMOKE AND AIR POLLUTION ALSO INCREASE RISK FOR HIGHER BP IN CHILD OFFSPRING. RECENT, BUT LIMITED, DATA INDICATE THAT ASSISTED REPRODUCTIVE TECHNOLOGIES CAN BE ASSOCIATED WITH HYPERTENSION IN CHILDHOOD, DESPITE OTHERWISE NORMAL GESTATION AND HEALTHY NEWBORN. GESTATIONAL EXPOSURES ASSOCIATED WITH HIGHER BP IN CHILDHOOD CAN BE RELATED TO FAMILIAL LIFESTYLE FACTORS, GENETICS, OR EPIGENETIC MODIFICATION OF FETAL DEOXYRIBONUCLEIC ACID (DNA). THESE FACTORS, OR COMBINATION OF FACTORS, AS WELL AS OTHER ADVERSE INTRAUTERINE CONDITIONS, COULD INDUCE FETAL PROGRAMING LEADING TO HEALTH CONSEQUENCES IN LATER LIFE. CURRENT AND DEVELOPING RESEARCH WILL PROVIDE ADDITIONAL INSIGHTS ON GESTATIONAL EXPOSURES AND FETAL ADJUSTMENTS THAT INCREASE RISK FOR HIGHER BP LEVELS IN CHILDHOOD.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
20  2605  28 EPIGENETICS-A POTENTIAL MEDIATOR BETWEEN AIR POLLUTION AND PRETERM BIRTH. PRETERM BIRTH IS A MAJOR CAUSE OF INFANT MORBIDITY AND MORTALITY AND A POTENTIAL RISK FACTOR FOR ADULT CHRONIC DISEASE. WITH OVER 15 MILLION INFANTS BORN PRETERM WORLDWIDE EACH YEAR, PRETERM BIRTH POSES A GLOBAL HEALTH CONCERN. THERE IS A POSSIBLE ASSOCIATION BETWEEN AIR POLLUTION AND PRETERM BIRTH, THOUGH STUDIES HAVE BEEN INCONSISTENT, LIKELY DUE TO VARIATION IN STUDY DESIGN. HOW AIR POLLUTION INDUCES HEALTH EFFECTS IS UNCERTAIN; HOWEVER, STUDIES HAVE REPEATEDLY DEMONSTRATED THE EFFECTS OF AIR POLLUTION ON EPIGENETIC MODIFICATIONS. MORE RECENT EVIDENCE SUGGESTS THAT EPIGENETICS MAY, IN TURN, BE LINKED TO PRETERM BIRTH. DISCOVERY OF ENVIRONMENTALLY MODIFIABLE EPIGENETIC PROCESSES CONNECTED TO PRETERM BIRTH MAY HELP TO IDENTIFY WOMEN AT RISK OF PRETERM BIRTH, AND ULTIMATELY LEAD TO DEVELOPMENT OF NEW PRETERM BIRTH PREVENTION MEASURES.	2016