1  6625 137 UNDERSTANDING RACIAL DISPARITIES OF PRETERM BIRTH THROUGH THE PLACENTA. THE RACIAL DISPARITY ASSOCIATED WITH PRETERM BIRTH IS A PUBLIC HEALTH CONCERN IN THE UNITED STATES. THE PLACENTA IS THE PRINCIPAL METABOLIC, RESPIRATORY, AND ENDOCRINE ORGAN OF THE FETUS AND A KEY ROUTE BY WHICH ENVIRONMENTAL EXPOSURES ARE TRANSMITTED FROM MOTHER TO OFFSPRING. AVAILABLE AT EVERY DELIVERY, IT MAY SERVE AS A MARKER OF DIFFERENCES IN PRENATAL EXPOSURES THAT MANIFEST DIFFERENTLY BY RACE. RECENTLY, WE DESCRIBED DIFFERENCES IN PLACENTAL PATHOLOGY BETWEEN AFRICAN-AMERICAN AND WHITE PRETERM BIRTHS: THE PREVALENCE OF CHRONIC INFLAMMATION WAS HIGHER AMONG AFRICAN-AMERICAN WOMEN'S PLACENTAS COMPARED WITH THOSE OF WHITE WOMEN. SIMILARLY, RACIAL DIFFERENCES HAVE BEEN SHOWN IN PLACENTAL MALPERFUSION AND PLACENTAL WEIGHT. SOCIAL DETERMINANTS SUCH AS POVERTY AND STRESS FROM DISCRIMINATION HAVE BEEN IMPLICATED IN RACIAL DISPARITIES IN PRETERM BIRTH. TO DATE, HOWEVER, THE UNDERLYING BIOLOGICAL MECHANISMS, WHETHER THROUGH INFLAMMATORY, OXIDATIVE STRESS, OR OTHER PATHWAYS INVOLVING EPIGENETIC PROGRAMMING, REMAIN LARGELY UNKNOWN. THE PLACENTA, COMPLEMENTED BY MATERNAL AND UMBILICAL CORD BLOOD BIOMARKERS, MAY PROVIDE IMPORTANT INFORMATION ON THE PERINATAL ENVIRONMENT THAT EXPLAINS THE ORIGINS OF RACIAL DISPARITIES IN PRETERM BIRTH RATES AND SUBSEQUENT HEALTH OUTCOMES. THIS ARTICLE REVIEWS EXISTING LITERATURE AND CURRENT RESEARCH GAPS. OPPORTUNITIES ARE DISCUSSED FOR FUTURE PLACENTAL RESEARCH THAT MAY REVEAL NOVEL MECHANISMS LEADING TO THE DEVELOPMENT OF NEW APPROACHES IN THE PREVENTION AND MANAGEMENT OF PRETERM BIRTH AND ITS OUTCOMES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
2  4504  33 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
3  4065  36 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
4  5192  38 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
5  2260  38 EPIGENETIC PROCESSES DURING PREECLAMPSIA AND EFFECTS ON FETAL DEVELOPMENT AND CHRONIC HEALTH. PREECLAMPSIA (PE), THE LEADING CAUSE OF MATERNAL AND FETAL MORBIDITY AND MORTALITY, IS ASSOCIATED WITH POOR FETAL GROWTH, INTRAUTERINE GROWTH RESTRICTION (IUGR) AND LOW BIRTH WEIGHT (LBW). OFFSPRING OF WOMEN WHO HAD PE ARE AT INCREASED RISK FOR CARDIOVASCULAR (CV) DISEASE LATER IN LIFE. HOWEVER, THE EXACT ETIOLOGY OF PE IS UNKNOWN. MOREOVER, THERE ARE NO EFFECTIVE INTERVENTIONS TO TREAT PE OR ALLEVIATE IUGR AND THE DEVELOPMENTAL ORIGINS OF CHRONIC DISEASE IN THE OFFSPRING. THE PLACENTA IS CRITICAL TO FETAL GROWTH AND DEVELOPMENT. EPIGENETIC REGULATORY PROCESSES SUCH AS HISTONE MODIFICATIONS, MICRORNAS AND DNA METHYLATION PLAY AN IMPORTANT ROLE IN PLACENTAL DEVELOPMENT INCLUDING CONTRIBUTIONS TO THE REGULATION OF TROPHOBLAST INVASION AND REMODELING OF THE SPIRAL ARTERIES. EPIGENETIC PROCESSES THAT LEAD TO CHANGES IN PLACENTAL GENE EXPRESSION IN PE MEDIATE DOWNSTREAM EFFECTS THAT CONTRIBUTE TO THE DEVELOPMENT OF PLACENTA DYSFUNCTION, A CRITICAL MEDIATOR IN THE ONSET OF PE, IMPAIRED FETAL GROWTH AND IUGR. THEREFORE, THIS REVIEW WILL FOCUS ON EPIGENETIC PROCESSES THAT CONTRIBUTE TO THE PATHOGENESIS OF PE AND IUGR. UNDERSTANDING THE EPIGENETIC MECHANISMS THAT CONTRIBUTE TO NORMAL PLACENTAL DEVELOPMENT AND THE INITIATING EVENTS IN PE MAY LEAD TO NOVEL THERAPEUTIC TARGETS IN PE THAT IMPROVE FETAL GROWTH AND MITIGATE INCREASED CV RISK IN THE OFFSPRING.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
6  5178  30 PREGNANCY AS A FUNDAMENTAL DETERMINANT OF CHILD HEALTH: A REVIEW. PURPOSE OF REVIEW: MATERNAL CONDITIONS AND EXPOSURES DURING PREGNANCY INCLUDING OVER- AND UNDERNUTRITION ARE ASSOCIATED WITH POOR CHILDBIRTH OUTCOMES, GROWTH, DEVELOPMENT AND CHRONIC CHILDHOOD DISEASES. WE EXAMINED CONTEMPORARY PREGNANCY-RELATED DETERMINANTS OF CHILD HEALTH. RECENT FINDINGS: WHILE MATERNAL UNDERNUTRITION REMAINS A MAJOR CONTRIBUTOR TO LOW BIRTH WEIGHT, MATERNAL OBESITY AFFECTS FOETAL GROWTH, BIRTH WEIGHT, SURVIVAL AND IS ASSOCIATED WITH CHILDHOOD OBESITY, ASTHMA AND AUTISTIC SPECTRUM DISORDERS. EMERGING EVIDENCE SUGGESTS THAT EPIGENETIC CHANGES, THE PRENATAL MICROBIOME AND MATERNAL IMMUNE ACTIVATION (MIA), A NEUROINFLAMMATORY PROCESS INDUCED BY DIET AND OTHER EXPOSURES CAUSE FOETAL PROGRAMMING RESULTING IN THESE CHRONIC CHILDHOOD DISEASES. MATERNAL DIET IS POTENTIALLY A MODIFIABLE RISK FACTOR FOR CONTROLLING LOW BIRTH WEIGHT, OBESITY AND CHRONIC DISEASE IN CHILDHOOD. FURTHER STUDIES ARE WARRANTED TO REFINE GUIDANCE ON DIETARY RESTRICTION AND PHYSICAL ACTIVITY DURING PREGNANCY AND DETERMINE HOW MIA AND PRENATAL MICROBIOTA CAN BE APPLIED TO CONTROL CHILDHOOD DISEASES ARISING FROM PROGRAMMING.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
7  5179  42 PREGNANCY: AN UNDERUTILIZED WINDOW OF OPPORTUNITY TO IMPROVE LONG-TERM MATERNAL AND INFANT HEALTH-AN APPEAL FOR CONTINUOUS FAMILY CARE AND INTERDISCIPLINARY COMMUNICATION. PHYSIOLOGIC ADAPTATIONS DURING PREGNANCY UNMASK A WOMAN'S PREDISPOSITION TO DISEASES. COMPLICATIONS ARE INCREASINGLY PREDICTED BY FIRST-TRIMESTER ALGORITHMS, AMPLIFY A PRE-EXISTING MATERNAL PHENOTYPE AND ACCELERATE RISKS FOR CHRONIC DISEASES IN THE OFFSPRING UP TO ADULTHOOD (BARKER HYPOTHESIS). RECENT EVIDENCE SUGGESTS THAT VICE VERSA, PREGNANCY DISEASES ALSO INDICATE MATERNAL AND EVEN GRANDPARENT'S RISKS FOR CHRONIC DISEASES (REVERSE BARKER HYPOTHESIS). PUB-MED AND EMBASE WERE REVIEWED FOR MESH TERMS "FETAL PROGRAMMING" AND "PREGNANCY COMPLICATIONS COMBINED WITH MATERNAL DISEASE" UNTIL JANUARY 2017. STUDIES LINKING PREGNANCY COMPLICATIONS TO FUTURE CARDIOVASCULAR, METABOLIC, AND THROMBOTIC RISKS FOR MOTHER AND OFFSPRING WERE REVIEWED. WOMEN WITH A HISTORY OF MISCARRIAGE, FETAL GROWTH RESTRICTION, PREECLAMPSIA, PRETERM DELIVERY, OBESITY, EXCESSIVE GESTATIONAL WEIGHT GAIN, GESTATIONAL DIABETES, SUBFERTILITY, AND THROMBOPHILIA MORE FREQUENTLY DEMONSTRATE WITH ECHOCARDIOGRAPHIC ABNORMALITIES, HIGHER FASTING INSULIN, DEVIATING LIPIDS OR CLOTTING FACTORS AND SHOW DEFECTIVE ENDOTHELIAL FUNCTION. THROMBOPHILIA HINTS TO THROMBOTIC RISKS IN LATER LIFE. PREGNANCY ABNORMALITIES CORRELATE WITH FUTURE CARDIOVASCULAR AND METABOLIC COMPLICATIONS AND EARLIER MORTALITY. CONVERSELY, WOMEN WITH A NORMAL PREGNANCY HAVE LOWER RATES OF SUBSEQUENT DISEASES THAN THE GENERAL FEMALE POPULATION CREATING THE TERM: "PREGNANCY AS A WINDOW FOR FUTURE HEALTH." ALTHOUGH THE PLACENTA WORKS AS A GATEKEEPER, MANY PREGNANCY COMPLICATIONS MAY LEAD TO SICKNESS AND EARLIER DEATH IN LATER LIFE WHEN THE CHILD BECOMES AN ADULT. THE EPIGENETIC MECHANISMS AND THE MISMATCH BETWEEN PRE- AND POSTNATAL LIFE HAVE CREATED THE TERM "FETAL ORIGIN OF ADULT DISEASE." UP TO NOW, THE IMPACT OF CARDIOVASCULAR, METABOLIC, OR THROMBOTIC RISK PROFILES HAS BEEN INVESTIGATED SEPARATELY FOR MOTHER AND CHILD. IN THIS MANUSCRIPT, WE STRIVE TO ILLUSTRATE THE CONSEQUENCES FOR BOTH, FETUS AND MOTHER WITHIN A COHESIVE PERSPECTIVE AND THUS TRY TO DEMONSTRATE THE COMPLEX INTERRELATIONSHIP OF GENETICS AND EPIGENETICS FOR LONG-TERM HEALTH OF SOCIETIES AND FUTURE GENERATIONS. MATERNAL-FETAL MEDICINE SPECIALISTS SHOULD HAVE A KEY ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES BY IMPLEMENTING A FRAMEWORK FOR PATIENT CONSULTATION AND INTERDISCIPLINARY NETWORKS. HEALTH-CARE PROVIDERS AND POLICY MAKERS SHOULD INCREASINGLY INVEST IN A STRATIFIED PRIMARY PREVENTION AND FOLLOW-UP TO REDUCE THE INCREASING NUMBER OF MANIFEST CARDIOVASCULAR AND METABOLIC DISEASES AND TO PREVENT WASTE OF HEALTH-CARE RESOURCES.	2017	

8  4066  33 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
9  3595  29 IMPLICATIONS OF MATERNAL CONDITIONS AND PREGNANCY COURSE ON OFFSPRING'S MEDICAL PROBLEMS IN ADULT LIFE. IN THE LAST DECADE, NUMEROUS EPIDEMIOLOGICAL, CLINICAL AND EXPERIMENTAL DATA SHOW THAT PERICONCEPTIONAL, PERINATAL AND POSTNATAL ENVIRONMENT DETERMINES THE OFFSPRING'S RISK FOR LATER-LIFE CHRONIC DISEASE. FOR THIS PHENOMENON, THE TERM "FETAL" OR "PERINATAL PROGRAMMING" IS USED. IN EXPOSED OFFSPRING ALREADY IN CHILDHOOD AND EARLY ADULTHOOD, METABOLIC AND CARDIOVASCULAR CHANGES CAN BE OBSERVED, LEADING TO OBESITY, DIABETES AND HYPERTENSION. NOWADAYS, THE MODE OF CONCEPTION (E.G., IN VITRO FERTILIZATION), MATERNAL METABOLIC CONDITIONS (E.G., UNDERNUTRITION, OVERNUTRITION, DIABETES) AND COMPLICATIONS DURING PREGNANCY (E.G., PREECLAMPSIA, INTRAUTERINE GROWTH RESTRICTION) ARE SUSPECTED TO BE NEGATIVE PREDICTORS FOR OFFSPRING'S LONG-TERM HEALTH. MECHANISMS RESPONSIBLE FOR THESE EFFECTS STILL REMAIN MAINLY UNCLEAR, BUT INCLUDE EPIGENETIC, TRANSCRIPTIONAL, ENDOPLASMIC RETICULUM STRESS, AND REACTIVE OXYGEN SPECIES. THIS REVIEW PRESENTS A PIECE OF THE PUZZLE WITH REGARDS TO PERICONCEPTIONAL AND EARLY PERINATAL CONDITIONS DETERMINING LATER-LIFE RISK FOR CHRONIC ADULT DISEASE.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
10   520  43 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
11  1098  32 COLLATERAL DAMAGE: MATERNAL OBESITY DURING PREGNANCY CONTINUES TO RISE. IMPORTANCE: THE PANDEMIC OF OBESITY DURING PREGNANCY NOW AFFLICTS 1 OUT OF EVERY 2 PREGNANT WOMEN IN THE UNITED STATES. EVEN THOUGH UNINTENDED PREGNANCY HAS DECREASED TO 45% OF ALL PREGNANCIES, 50% OF THOSE UNINTENDED PREGNANCIES OCCUR IN OBESE WOMEN. OBJECTIVE: THIS STUDY AIMS TO IDENTIFY WHY CURRENT LIFESTYLE INTERVENTIONS FOR OBESE PREGNANCY ARE NOT EFFECTIVE AND WHAT THE NEWER COMPLICATIONS ARE FOR OBESITY DURING PREGNANCY. EVIDENCE ACQUISITION: AVAILABLE LITERATURES ON CURRENT TREATMENTS FOR MATERNAL OBESITY WERE REVIEWED FOR EFFECTIVENESS. EMERGING MATERNAL AND INFANT COMPLICATIONS FROM OBESITY DURING PREGNANCY WERE EXAMINED FOR SIGNIFICANCE. RESULTS: LIMITATIONS IN SUCCESSFUL INTERVENTIONS FELL INTO 3 BASIC CATEGORIES TO INCLUDE THE FOLLOWING: (1) PRECONCEPTION WEIGHT LOSS; (2) BARIATRIC SURGERY BEFORE PREGNANCY; AND (3) PREVENTION OF EXCESSIVE GESTATIONAL WEIGHT GAIN DURING PREGNANCY. EMERGING SIGNIFICANT PHYSIOLOGICAL CHANGES FROM MATERNAL OBESITY IS COMPOSED OF INFLAMMATION (PLACENTA AND HUMAN MILK), METABOLISM (HORMONES, MICROBIOME, FATTY ACIDS), AND OFFSPRING OUTCOMES (BODY COMPOSITION, CONGENITAL MALFORMATIONS, CHRONIC KIDNEY DISEASE, ASTHMA, NEURODEVELOPMENT, AND BEHAVIOR). CONCLUSIONS AND RELEVANCE: ARE CURRENT PREPREGNANCY LIFESTYLE AND BEHAVIORAL INTERVENTIONS FEASIBLE TO PREVENT MATERNAL OBESITY COMPLICATIONS? EPIGENETIC AND METABOLOMIC RESEARCH WILL BE CRITICAL TO DETERMINE WHAT IS NEEDED TO BLUNT THE EFFECTS OF MATERNAL OBESITY AND TO DISCOVER SUCCESSFUL TREATMENT.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
12  3578  30 IMPACT OF PARENTAL OVER- AND UNDERWEIGHT ON THE HEALTH OF OFFSPRING. PARENTAL EXCESS WEIGHT AND ESPECIALLY PREGESTATIONAL MATERNAL OBESITY AND EXCESSIVE WEIGHT GAIN DURING PREGNANCY HAVE BEEN RELATED TO AN INCREASED RISK OF METABOLIC (OBESITY, TYPE 2 DIABETES, CARDIOVASCULAR DISEASE, METABOLIC SYNDROME) AND NONMETABOLIC (CANCER, OSTEOPOROSIS, ASTHMA, NEUROLOGIC ALTERATIONS) DISEASES IN THE OFFSPRING, PROBABLY MEDIATED BY EPIGENETIC MECHANISMS OF FETAL PROGRAMMING. MATERNAL UNDERWEIGHT IS LESS COMMON IN DEVELOPED SOCIETIES, BUT THE DISCREPANCY BETWEEN A POOR NUTRITIONAL ENVIRONMENT IN UTERO AND A NORMAL OR EXCESSIVE POSTNATAL FOOD SUPPLY WITH RAPID GROWTH CATCH-UP APPEARS TO BE THE MAIN CANDIDATE MECHANISM OF THE DEVELOPMENT OF CHRONIC DISEASES DURING THE OFFSPRING'S ADULTHOOD. THE ROLE OF THE POSTNATAL ENVIRONMENT IN BOTH SCENARIOS (PARENTAL OVERWEIGHT OR UNDERWEIGHT) ALSO SEEMS TO INFLUENCE THE OFFSPRING'S HEALTH. LIFESTYLE INTERVENTIONS BEFORE AND DURING PREGNANCY IN BOTH PARENTS, BUT ESPECIALLY IN THE MOTHER, AS WELL AS IN CHILDREN AFTER BIRTH, ARE ADVISABLE TO COUNTERACT THE MANY UNDESIRABLE CHRONIC CONDITIONS DESCRIBED.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
13  6724  38 VITAMIN D: EFFECTS ON PREGNANCY, MATERNAL, FETAL AND POSTNATAL OUTCOMES. A HIGH PREVALENCE OF VITAMIN D DEFICIENCY AND ITS NEGATIVE CONSEQUENCES FOR HEALTH IS IDENTIFIED AS AREA OF PRIMARY CONCERN FOR SCIENTISTS AND CLINICIANS WORLDWIDE. VITAMIN D DEFICIENCY AFFECTS NOT ONLY BONE HEALTH BUT MANY SOCIALLY SIGNIFICANT ACUTE AND CHRONIC DISEASES. OBSERVATIONAL STUDIES SUPPORT THAT PREGNANT AND LACTATING WOMEN, CHILDREN AND TEENAGERS REPRESENT THE HIGH RISK GROUPS FOR DEVELOPING VITAMIN D DEFICIENCY. CURRENT EVIDENCE HIGHLIGHTS A CRUCIAL ROLE OF VITAMIN D IN PROVIDING THE FETAL LIFE-SUPPORT SYSTEM AND FETUS DEVELOPMENT, INCLUDING IMPLANTATION, PLACENTAL FORMATION, INTRA- AND POSTPARTUM PERIODS. HYPOVITAMINOSIS D DURING PREGNANCY IS ASSOCIATED WITH A HIGHER INCIDENCE OF PLACENTAL INSUFFICIENCY, SPONTANEOUS ABORTIONS AND PRETERM BIRTH, PREECLAMPSIA, GESTATIONAL DIABETES, IMPAIRED FETAL AND CHILDHOOD GROWTH, INCREASED RISK OF AUTOIMMUNE DISEASES FOR OFFSPRINGS. POTENTIAL MECHANISMS FOR THE OBSERVED ASSOCIATIONS CONTAIN METABOLIC, IMMUNOMODULATORY AND ANTIINFLAMMATORY EFFECTS OF VITAMIN D. EPIGENETIC MODIFICATIONS IN VITAMIN D-ASSOCIATED GENES AND FETAL PROGRAMMING ARE OF PARTICULAR INTEREST. THE CONCEPT OF PREVENTING VITAMIN D DEFICIENCY IS ACTIVELY DISCUSSED, INCLUDING SUPPLEMENTATION IN DIFFERENT ETHNIC GROUPS, REQUIRED DOSES, TIME OF INITIATION AND THERAPY DURATION, INFLUENCE ON GESTATION AND CHILDBIRTH. AN ADEQUATE SUPPLY OF VITAMIN D DURING PREGNANCY IMPROVES THE MATERNAL AND FETAL OUTCOMES, SHORT AND LONG TERM HEALTH OF THE OFFSPRING. STILL CURRENT DATA ON RELATIONSHIP BETWEEN MATERNAL VITAMIN D STATUS AND PREGNANCY OUTCOMES REMAINS CONTROVERSIAL. THE LARGE OBSERVATIONAL AND INTERVENTIONAL RANDOMIZED CONTROL TRIALS ARE REQUIRED TO CREATE EVIDENCE-BASED GUIDELINES FOR THE SUPPLEMENTATION OF VITAMIN D IN PREGNANT AND LACTATING WOMEN.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
14  6279  33 THE PLACENTA AS A TARGET OF EPIGENETIC ALTERATIONS IN WOMEN WITH GESTATIONAL DIABETES MELLITUS AND POTENTIAL IMPLICATIONS FOR THE OFFSPRING. GESTATIONAL DIABETES MELLITUS (GDM) IS A PREGNANCY COMPLICATION FIRST DETECTED IN THE SECOND OR THIRD TRIMESTER IN WOMEN THAT DID NOT SHOW EVIDENT GLUCOSE INTOLERANCE OR DIABETES BEFORE GESTATION. IN 2019, THE INTERNATIONAL DIABETES FEDERATION REPORTED THAT 15.8% OF LIVE BIRTHS WERE AFFECTED BY HYPERGLYCEMIA DURING PREGNANCY, OF WHICH 83.6% WERE DUE TO GESTATIONAL DIABETES MELLITUS, 8.5% WERE DUE TO DIABETES FIRST DETECTED IN PREGNANCY, AND 7.9% WERE DUE TO DIABETES DETECTED BEFORE PREGNANCY. GDM INCREASES THE SUSCEPTIBILITY TO DEVELOPING CHRONIC DISEASES FOR BOTH THE MOTHER AND THE BABY LATER IN LIFE. UNDER GDM CONDITIONS, THE INTRAUTERINE ENVIRONMENT BECOMES HYPERGLYCEMIC, WHILE ALSO SHOWING HIGH CONCENTRATIONS OF FATTY ACIDS AND PROINFLAMMATORY CYTOKINES, PRODUCING MORPHOLOGICAL, STRUCTURAL, AND MOLECULAR MODIFICATIONS IN THE PLACENTA, AFFECTING ITS FUNCTION; THESE ALTERATIONS MAY PREDISPOSE THE BABY TO DISEASE IN ADULT LIFE. MOLECULAR ALTERATIONS INCLUDE EPIGENETIC MECHANISMS SUCH AS DNA AND RNA METHYLATION, CHROMATIN REMODELING, HISTONE MODIFICATIONS, AND EXPRESSION OF NONCODING RNAS (NCRNAS). THE PLACENTA IS A UNIQUE ORGAN THAT ORIGINATES ONLY IN PREGNANCY, AND ITS MAIN FUNCTION IS COMMUNICATION BETWEEN THE MOTHER AND THE FETUS, ENSURING HEALTHY DEVELOPMENT. THUS, THIS REVIEW PROVIDES UP-TO-DATE INFORMATION REGARDING TWO OF THE BEST-DOCUMENTED (EPIGENETIC) MECHANISMS (DNA METHYLATION AND MIRNA EXPRESSION) ALTERED IN THE HUMAN PLACENTA UNDER GDM CONDITIONS, AS WELL AS POTENTIAL IMPLICATIONS FOR THE OFFSPRING.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
15  5430  26 REGULATORS INVOLVED IN TROPHOBLAST SYNCYTIALIZATION IN THE PLACENTA OF INTRAUTERINE GROWTH RESTRICTION. PLACENTAL DYSFUNCTION REFERS TO THE INSUFFICIENCY OF PLACENTAL PERFUSION AND CHRONIC HYPOXIA DURING EARLY PREGNANCY, WHICH IMPAIRS PLACENTAL FUNCTION AND CAUSES INADEQUATE SUPPLY OF OXYGEN AND NUTRIENTS TO THE FETUS, AFFECTING FETAL DEVELOPMENT AND HEALTH. FETAL INTRAUTERINE GROWTH RESTRICTION, ONE OF THE MOST COMMON OUTCOMES OF PREGNANCY-INDUCED HYPERTENSIONS, CAN BE CAUSED BY PLACENTAL DYSFUNCTION, RESULTING FROM DEFICIENT TROPHOBLAST SYNCYTIALIZATION, INADEQUATE TROPHOBLAST INVASION AND IMPAIRED VASCULAR REMODELING. DURING PLACENTAL DEVELOPMENT, CYTOTROPHOBLASTS FUSE TO FORM A MULTINUCLEATED SYNCYTIA BARRIER, WHICH SUPPLIES OXYGEN AND NUTRIENTS TO MEET THE METABOLIC DEMANDS FOR FETAL GROWTH. A REDUCTION IN THE CELL FUSION INDEX AND THE NUMBER OF NUCLEI IN THE SYNCYTIOTROPHOBLAST ARE FOUND IN THE PLACENTAS OF PREGNANCIES COMPLICATED BY IUGR, SUGGESTING THAT THE OCCURRENCE OF IUGR MAY BE RELATED TO INADEQUATE TROPHOBLAST SYNCYTIALIZATION. DURING THE MULTIPLE PROCESSES OF TROPHOBLASTS SYNCYTIALIZATION, SPECIFIC PROTEINS AND SEVERAL SIGNALING PATHWAYS ARE INVOLVED IN COORDINATING THESE EVENTS AND REGULATING PLACENTAL FUNCTION. IN ADDITION, EPIGENETIC MODIFICATIONS, CELL METABOLISM, SENESCENCE, AND AUTOPHAGY ARE ALSO INVOLVED. STUDY FINDINGS HAVE INDICATED SEVERAL ABNORMALLY EXPRESSED SYNCYTIALIZATION-RELATED PROTEINS AND SIGNALING PATHWAYS IN THE PLACENTAS OF PREGNANCIES COMPLICATED BY IUGR, SUGGESTING THAT THESE ELEMENTS MAY PLAY A CRUCIAL ROLE IN THE OCCURRENCE OF IUGR. IN THIS REVIEW, WE DISCUSS THE REGULATORS OF TROPHOBLAST SYNCYTIALIZATION AND THEIR ABNORMAL EXPRESSION IN THE PLACENTAS OF PREGNANCIES COMPLICATED BY IUGR.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
16  6270  39 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	
                                                                                                                                 
17   167  40 ABNORMAL PLACENTATION ASSOCIATED WITH INFERTILITY AS A MARKER OF OVERALL HEALTH. INFERTILITY AND THE FERTILITY TREATMENTS UTILIZED ARE ASSOCIATED WITH ABNORMAL PLACENTATION LEADING TO ADVERSE PREGNANCY OUTCOMES RELATED TO PLACENTATION, INCLUDING PRETERM BIRTH, LOW BIRTH WEIGHT, PLACENTA ACCRETE AND PLACENTA PREVIA. THIS MAY BE DUE TO THE UNDERLYING GENETICS PREDISPOSING TO INFERTILITY OR THE EPIGENETIC CHANGES ASSOCIATED WITH THE FERTILITY TREATMENTS UTILIZED, AS SPECIFIC DISEASE STATES LEADING TO INFERTILITY ARE AT INCREASED RISK OF ADVERSE OUTCOMES, INCLUDING PLACENTAL ABRUPTION, FETAL LOSS, GDM, AND OUTCOMES RELATED TO PLACENTATION, AS WELL AS THE TREATMENTS UTILIZED INCLUDING IN VITRO FERTILIZATION (IVF) AND NIFT (NON-IVF FERTILITY TREATMENT). PLACENTATION DEFECTS, LEADING TO ADVERSE MATERNAL AND FETAL OUTCOMES, WHICH ARE MORE PRONOUNCED IN THE INFERTILE POPULATION, OCCUR DUE TO CHANGES IN TROPHOBLAST INVASION, VASCULAR DEFECTS, CHANGES IN THE ENVIRONMENTAL MILIEU, CHRONIC INFLAMMATION AND OXIDATIVE STRESS. THESE SIMILAR PROCESSES ARE RECOGNIZED AS MAJOR CONTRIBUTORS TO LIFELONG RISK OF CARDIOVASCULAR AND METABOLIC DISEASE FOR BOTH THE MOTHER AND HER OFFSPRING. THUS, ABNORMAL PLACENTATION, FOUND TO BE MORE PREVALENT IN THE INFERTILE POPULATION, MAY BE THE KEY TO BETTER UNDERSTAND HOW INFERTILITY AFFECTS OVERALL AND LONG TERM HEALTH.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
18  2511  38 EPIGENETICS AND PREECLAMPSIA: PROGRAMMING OF FUTURE OUTCOMES. PREGNANCY IS KNOWN TO INDUCE RAPID, PROGRESSIVE, AND SUBSTANTIAL CHANGES TO THE CARDIOVASCULAR SYSTEM, ULTIMATELY FACILITATING SUCCESSFUL PREGNANCY OUTCOMES. WOMEN WHO DEVELOP HYPERTENSIVE DISORDERS DURING PREGNANCY ARE CONSIDERED TO HAVE "FAILED" THE CARDIOVASCULAR STRESS TEST OF PREGNANCY AND LIKELY REPRESENT A SUBPOPULATION WITH INADEQUATE CARDIOVASCULAR ACCOMMODATION. PREECLAMPSIA IS A SERIOUS COMPLICATION WITH A MYRIAD OF MANIFESTATIONS IN BOTH MOTHER AND OFFSPRING. THIS PREGNANCY SYNDROME IS A POLYGENIC DISEASE AND HAS NOW BEEN LINKED TO A GREATER INCIDENCE OF CARDIOVASCULAR DISEASE. MOREOVER, OFFSPRINGS BORN TO PREECLAMPTIC MOTHERS EXHIBIT AN ELEVATED RISK OF CARDIOVASCULAR DISEASE, STROKE, AND MENTAL DISORDERS DURING ADULTHOOD. THIS SUGGESTS THAT PREECLAMPSIA NOT ONLY EXPOSES THE MOTHER AND THE FETUS TO COMPLICATIONS DURING PREGNANCY BUT ALSO PROGRAMS CHRONIC DISEASES DURING ADULTHOOD IN THE OFFSPRING. THE ETIOLOGY OF PREECLAMPSIA REMAINS UNKNOWN, WITH VARIOUS THEORIES BEING SUGGESTED TO EXPLAIN ITS ORIGIN. IT IS PRIMARILY THOUGHT TO BE ASSOCIATED WITH POOR PLACENTATION AND ENTAILS EXCESSIVE MATERNAL INFLAMMATION AND ENDOTHELIAL DYSFUNCTION. IT IS WELL ESTABLISHED NOW THAT THE MATERNAL IMMUNE SYSTEM AND THE PLACENTA ARE INVOLVED IN A HIGHLY CHOREOGRAPHED CROSS TALK THAT UNDERLIES ADEQUATE SPIRAL ARTERY REMODELING REQUIRED FOR UTEROPLACENTAL PERFUSION AND FREE FLOW OF NUTRIENTS TO THE FETUS. ALTHOUGH IT IS NOT CLEAR WHETHER IMMUNOLOGICAL ALTERATIONS OCCUR EARLY DURING PREGNANCY, STUDIES HAVE PROPOSED THAT DYSREGULATED SYSTEMIC AND PLACENTAL IMMUNITY CONTRIBUTE TO IMPAIRED ANGIOGENESIS AND THE ONSET OF PREECLAMPSIA. RECENTLY EMERGED STRONG EVIDENCE SUGGESTS A POTENTIAL LINK AMONG EPIGENETICS, MICRORNAS (MIRNAS), AND PREGNANCY COMPLICATIONS. THIS CHAPTER WILL FOCUS ON IMPORTANT ASPECTS OF EPIGENETICS, IMMUNOLOGICAL ASPECTS, AND CARDIOVASCULAR AND VASCULAR REMODELING OF PREECLAMPSIA.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
19  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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
20   418  43 ANCESTRAL EXPOSURE TO STRESS EPIGENETICALLY PROGRAMS PRETERM BIRTH RISK AND ADVERSE MATERNAL AND NEWBORN OUTCOMES. BACKGROUND: CHRONIC STRESS IS CONSIDERED TO BE ONE OF MANY CAUSES OF HUMAN PRETERM BIRTH (PTB), BUT NO DIRECT EVIDENCE HAS YET BEEN PROVIDED. HERE WE SHOW IN RATS THAT STRESS ACROSS GENERATIONS HAS DOWNSTREAM EFFECTS ON ENDOCRINE, METABOLIC AND BEHAVIOURAL MANIFESTATIONS OF PTB POSSIBLY VIA MICRORNA (MIRNA) REGULATION. METHODS: PREGNANT DAMS OF THE PARENTAL GENERATION WERE EXPOSED TO STRESS FROM GESTATIONAL DAYS 12 TO 18. THEIR PREGNANT DAUGHTERS (F1) AND GRAND-DAUGHTERS (F2) EITHER WERE STRESSED OR REMAINED AS NON-STRESSED CONTROLS. GESTATIONAL LENGTH, MATERNAL GESTATIONAL WEIGHT GAIN, BLOOD GLUCOSE AND PLASMA CORTICOSTERONE LEVELS, LITTER SIZE AND OFFSPRING WEIGHT GAIN FROM POSTNATAL DAYS 1 TO 30 WERE RECORDED IN EACH GENERATION, INCLUDING F3. MATERNAL BEHAVIOURS WERE ANALYSED FOR THE FIRST HOUR AFTER COMPLETED PARTURITION, AND OFFSPRING SENSORIMOTOR DEVELOPMENT WAS RECORDED ON POSTNATAL DAY (P) 7. F0 THROUGH F2 MATERNAL BRAIN FRONTAL CORTEX, UTERUS AND PLACENTA MIRNA AND GENE EXPRESSION PATTERNS WERE USED TO IDENTIFY STRESS-INDUCED EPIGENETIC REGULATORY PATHWAYS OF MATERNAL BEHAVIOUR AND PREGNANCY MAINTENANCE. RESULTS: PROGRESSIVELY UP TO THE F2 GENERATION, STRESS GRADUALLY REDUCED GESTATIONAL LENGTH, MATERNAL WEIGHT GAIN AND BEHAVIOURAL ACTIVITY, AND INCREASED BLOOD GLUCOSE LEVELS. REDUCED OFFSPRING GROWTH AND DELAYED BEHAVIOURAL DEVELOPMENT IN THE STRESS COHORT WAS RECOGNIZABLE AS EARLY AS P7, WITH THE GREATEST EFFECT IN THE F3 OFFSPRING OF TRANSGENERATIONALLY STRESSED MOTHERS. FURTHERMORE, STRESS ALTERED MIRNA EXPRESSION PATTERNS IN THE BRAIN AND UTERUS OF F2 MOTHERS, INCLUDING THE MIR-200 FAMILY, WHICH REGULATES PATHWAYS RELATED TO BRAIN PLASTICITY AND PARTURITION, RESPECTIVELY. MAIN MIR-200 FAMILY TARGET GENES IN THE UTERUS, STAT5B, ZEB1 AND ZEB2, WERE DOWNREGULATED BY MULTIGENERATIONAL STRESS IN THE F1 GENERATION. ZEB2 WAS ALSO REDUCED IN THE STRESSED F2 GENERATION, SUGGESTING A CAUSAL MECHANISM FOR DISTURBED PREGNANCY MAINTENANCE. ADDITIONALLY, STRESS INCREASED PLACENTAL MIR-181A, A MARKER OF HUMAN PTB. CONCLUSIONS: THE FINDINGS INDICATE THAT A FAMILY HISTORY OF STRESS MAY PROGRAM CENTRAL AND PERIPHERAL PATHWAYS REGULATING GESTATIONAL LENGTH AND MATERNAL AND NEWBORN HEALTH OUTCOMES IN THE MATERNAL LINEAGE. THIS NEW PARADIGM MAY MODEL THE ORIGIN OF MANY HUMAN PTB CAUSES.	2014