1 6279 128 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 2 3118 50 GESTATIONAL DIABETES MELLITUS: GENETIC FACTORS, EPIGENETIC ALTERATIONS, AND MICROBIAL COMPOSITION. GESTATIONAL DIABETES MELLITUS (GDM) IS A COMMON METABOLIC DISORDER, USUALLY DIAGNOSED DURING THE THIRD TRIMESTER OF PREGNANCY THAT USUALLY DISAPPEARS AFTER DELIVERY. IN GDM, THE EXCESS OF GLUCOSE, FATTY ACIDS, AND AMINO ACIDS RESULTS IN FOETUSES LARGE FOR GESTATIONAL AGE. HYPERGLYCAEMIA AND INSULIN RESISTANCE ACCELERATE THE METABOLISM, RAISING THE OXYGEN DEMAND, AND CREATING CHRONIC HYPOXIA AND INFLAMMATION. WOMEN WHO EXPERIENCED GDM AND THEIR OFFSPRING ARE AT RISK OF DEVELOPING TYPE-2 DIABETES, OBESITY, AND OTHER METABOLIC OR CARDIOVASCULAR CONDITIONS LATER IN LIFE. GENETIC FACTORS MAY PREDISPOSE THE DEVELOPMENT OF GDM; HOWEVER, THEY DO NOT ACCOUNT FOR ALL GDM CASES; LIFESTYLE AND DIET ALSO PLAY IMPORTANT ROLES IN GDM DEVELOPMENT BY MODULATING EPIGENETIC SIGNATURES AND THE BODY'S MICROBIAL COMPOSITION; THEREFORE, THIS IS A CONDITION WITH A COMPLEX, MULTIFACTORIAL AETIOLOGY. IN THIS CONTEXT, WE REVISED PUBLISHED REPORTS DESCRIBING GDM-ASSOCIATED SINGLE-NUCLEOTIDE POLYMORPHISMS (SNPS), DNA METHYLATION AND MICRORNA EXPRESSION IN DIFFERENT TISSUES (SUCH AS PLACENTA, UMBILICAL CORD, ADIPOSE TISSUE, AND PERIPHERAL BLOOD), AND MICROBIAL COMPOSITION IN THE GUT, ORAL CAVITY, AND VAGINA FROM PREGNANT WOMEN WITH GDM, AS WELL AS THE BACTERIAL COMPOSITION OF THE OFFSPRING. ALTOGETHER, THESE REPORTS INDICATE THAT A NUMBER OF SNPS ARE ASSOCIATED TO GDM PHENOTYPES AND MAY PREDISPOSE THE DEVELOPMENT OF THE DISEASE. HOWEVER, EXTRINSIC FACTORS (LIFESTYLE, NUTRITION) MODULATE, THROUGH EPIGENETIC MECHANISMS, THE RISK OF DEVELOPING THE DISEASE, AND SOME ASSOCIATION EXISTS BETWEEN THE MICROBIAL COMPOSITION WITH GDM IN AN ORGAN-SPECIFIC MANNER. GENES, EPIGENETIC SIGNATURES, AND MICROBIOTA COULD BE TRANSFERRED TO THE OFFSPRING, INCREASING THE POSSIBILITY OF DEVELOPING CHRONIC DEGENERATIVE CONDITIONS THROUGH POSTNATAL LIFE. 2023 3 4782 41 NUTRIGENETICS, EPIGENETICS AND GESTATIONAL DIABETES: CONSEQUENCES IN MOTHER AND CHILD. GESTATIONAL DIABETES MELLITUS (GDM) IS THE MOST COMMON METABOLIC CONDITION DURING PREGNANCY AND MAY RESULT IN SHORT- AND LONG-TERM COMPLICATIONS FOR BOTH MOTHER AND OFFSPRING. THE COMPLEXITY OF PHENOTYPIC OUTCOMES SEEMS INFLUENCED BY GENETIC SUSCEPTIBILITY, NUTRIENT-GENE INTERACTIONS AND LIFESTYLE INTERACTING WITH CLINICAL FACTORS. THERE IS STRONG EVIDENCE THAT NOT ONLY THE ADVERSE GENETIC BACKGROUND BUT ALSO THE EPIGENETIC MODIFICATIONS IN RESPONSE TO NUTRITIONAL AND ENVIRONMENTAL FACTORS COULD INFLUENCE THE MATERNAL HYPERGLYCEMIA IN PREGNANCY AND THE FOETAL METABOLIC PROGRAMMING. IN THIS VIEW, THE CORRELATION BETWEEN EPIGENETIC MODIFICATIONS AND THEIR TRANSGENERATIONAL EFFECTS REPRESENTS A VERY INTERESTING FIELD OF STUDY. THE PRESENT REVIEW GIVES INSIGHT INTO THE ROLE OF GENE VARIANTS AND THEIR INTERACTIONS WITH NUTRIENTS IN GDM. IN ADDITION, WE PROVIDE AN OVERVIEW OF THE EPIGENETIC CHANGES AND THEIR ROLE IN THE MATERNAL-FOETAL TRANSMISSION OF CHRONIC DISEASES. OVERALL, THE KNOWLEDGE OF EPIGENETIC MODIFICATIONS INDUCED BY AN ADVERSE INTRAUTERINE AND PERINATAL ENVIRONMENT COULD SHED LIGHT ON THE POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS OF LONG-TERM DISEASE DEVELOPMENT IN THE OFFSPRING AND PROVIDE USEFUL TOOLS FOR THEIR PREVENTION. 2019 4 6099 42 THE EMERGING ROLE OF BIOMARKERS IN THE DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS. GESTATIONAL DIABETES MELLITUS (GDM) IS A COMMON COMPLICATION OF PREGNANCY; ITS RISING INCIDENCE IS A RESULT OF INCREASED MATERNAL OBESITY AND OLDER MATERNAL AGE TOGETHER WITH ALTERED DIAGNOSTIC CRITERIA IDENTIFYING A GREATER PROPORTION OF PREGNANT WOMEN WITH GDM. ITS CONSEQUENCES ARE FAR-REACHING, ASSOCIATED WITH POORER MATERNAL AND NEONATAL OUTCOMES COMPARED TO NON-GDM PREGNANCIES, AND GDM HAS IMPLICATIONS FOR METABOLIC HEALTH IN BOTH MOTHER AND OFFSPRING. OBJECTIVE MARKERS TO IDENTIFY WOMEN AT HIGH RISK FOR THE DEVELOPMENT OF GDM ARE USEFUL TO TARGET THERAPY AND POTENTIALLY PREVENT ITS DEVELOPMENT. ESTABLISHED CLINICAL RISK FACTORS FOR GDM INCLUDE OVERWEIGHT/OBESITY, AGE, ETHNICITY, AND FAMILY HISTORY OF DIABETES, THOUGH THEY LACK SPECIFICITY FOR ITS DEVELOPMENT. THE ADDITION OF BIOMARKERS TO PREDICTIVE MODELS OF GDM MAY IMPROVE THE ABILITY TO IDENTIFY WOMEN AT RISK OF GDM PRIOR TO ITS DEVELOPMENT. THESE BIOMARKERS REFLECT THE PATHOPHYSIOLOGIC MECHANISMS OF GDM INVOLVING INSULIN RESISTANCE, CHRONIC INFLAMMATION, AND ALTERED PLACENTAL FUNCTION. IN ADDITION, THE ROLE OF EPIGENETIC CHANGES IN GDM PATHOGENESIS HIGHLIGHTS THE COMPLEX INTERPLAY BETWEEN GENETIC AND ENVIRONMENTAL FACTORS, POTENTIALLY OFFERING FURTHER REFINEMENT OF THE PREDICTION OF GDM RISK. IN THIS REVIEW, WE WILL DISCUSS THE CLINICAL CHALLENGES ASSOCIATED WITH THE DIAGNOSIS OF GDM AND ITS CURRENT PATHOPHYSIOLOGIC BASIS, GIVING RISE TO POTENTIAL BIOMARKERS THAT MAY AID IN ITS IDENTIFICATION. WHILE NOT YET VALIDATED FOR CLINICAL USE, WE EXPLORE THE POSSIBLE CLINICAL ROLE OF BIOMARKERS IN THE FUTURE. WE ALSO EXPLORE NOVEL DIAGNOSTIC TOOLS, INCLUDING HIGH THROUGHPUT METHODOLOGIES, THAT MAY HAVE POTENTIAL FUTURE APPLICATION IN THE IDENTIFICATION OF WOMEN WITH GDM. 2018 5 3572 43 IMPACT OF MATERNAL DIABETES ON EPIGENETIC MODIFICATIONS LEADING TO DISEASES IN THE OFFSPRING. GESTATIONAL DIABETES, OCCURRING DURING THE HYPERGLYCEMIC PERIOD OF PREGNANCY IN MATERNAL LIFE, IS A PATHOLOGIC STATE THAT INCREASES THE INCIDENCE OF COMPLICATIONS IN BOTH MOTHER AND FETUS. OFFSPRING THUS EXPOSED TO AN ADVERSE FETAL AND EARLY POSTNATAL ENVIRONMENT MAY MANIFEST INCREASED SUSCEPTIBILITY TO A NUMBER OF CHRONIC DISEASES LATER IN LIFE. COMPELLING EVIDENCE FOR THE ROLE OF EPIGENETIC TRANSMISSION IN THESE COMPLICATIONS HAS COME FROM COMPARISON OF SIBLINGS BORN BEFORE AND AFTER THE DEVELOPMENT OF MATERNAL DIABETES, EXPOSURE TO THIS INTRAUTERINE DIABETIC ENVIRONMENT BEING SHOWN TO CAUSE ALTERATIONS IN FETAL GROWTH PATTERNS WHICH PREDISPOSE THESE INFANTS TO DEVELOPING OVERWEIGHT AND OBESITY LATER IN LIFE. DIABETES OF THE OFFSPRING IS ALSO MAINLY THE CONSEQUENCE OF EXPOSURE TO THE DIABETIC INTRAUTERINE ENVIRONMENT, IN ADDITION TO GENETIC SUSCEPTIBILITY. SINCE OBESITY AND DIABETES ARE KNOWN TO INCREASE THE RISK OF CARDIOVASCULAR DISEASE, CARDIOVASCULAR SEQUELAE IN THE OFFSPRING OF DIABETIC MOTHERS ARE VIRTUALLY INEVITABLE. RESEARCH DATA ALSO SUGGEST THAT EXPOSURE TO A DIABETIC INTRAUTERINE ENVIRONMENT DURING PREGNANCY IS ASSOCIATED WITH AN INCREASE IN DYSLIPIDEMIA, SUBCLINICAL VASCULAR INFLAMMATION, AND ENDOTHELIAL DYSFUNCTION PROCESSES IN THE OFFSPRING, ALL OF WHICH ARE LINKED WITH DEVELOPMENT OF CARDIOVASCULAR DISEASE LATER IN LIFE. THE MAIN UNDERLYING MECHANISMS INVOLVE PERSISTENT HYPERGLYCEMIA HYPERINSULINEMIA AND LEPTIN RESISTANCE. 2012 6 2267 37 EPIGENETIC PROGRAMMING OF OBESITY AND DIABETES BY IN UTERO EXPOSURE TO GESTATIONAL DIABETES MELLITUS. IT IS NOW WELL ACCEPTED THAT OFFSPRING EXPOSED TO MATERNAL UNDERNUTRITION, OBESITY, OR GESTATIONAL DIABETES MELLITUS HAVE AN INCREASED RISK FOR CHRONIC DISEASES LATER IN LIFE, SUPPORTING THE THEORY OF THE EARLY ORIGINS OF CHRONIC DISEASES. HOWEVER, THE MOLECULAR MECHANISMS THROUGH WHICH THE EXPOSURE TO AN ALTERED IN UTERO ENVIRONMENT TRANSLATES INTO THE DEVELOPMENT OF CHRONIC DISEASES ARE NOT YET WELL UNDERSTOOD. RECENTLY REPORTED PROMISING RESULTS HELP TO RESOLVE THIS ISSUE. THEY SUGGEST THAT EPIGENETIC MODIFICATIONS ARE A POTENTIAL MECHANISM FOR FETAL METABOLIC PROGRAMMING. THIS REVIEW PROVIDES AN OVERVIEW OF THE RELATIONSHIP BETWEEN THE EXPOSURE TO AN ALTERED INTRAUTERINE ENVIRONMENT AND FETAL METABOLIC PROGRAMMING, FOCUSING ON GESTATIONAL DIABETES MELLITUS AND EPIGENETIC VARIATIONS AT ADIPOKINE CANDIDATE GENES. 2013 7 3707 35 INFLUENCE OF MATERNAL OVERNUTRITION AND GESTATIONAL DIABETES ON THE PROGRAMMING OF METABOLIC HEALTH OUTCOMES IN THE OFFSPRING: EXPERIMENTAL EVIDENCE. THE INCIDENCE OF OBESITY AND TYPE 2 DIABETES MELLITUS HAVE RISEN ACROSS THE WORLD DURING THE PAST FEW DECADES AND HAS ALSO REACHED AN ALARMING LEVEL AMONG CHILDREN. IN ADDITION, WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. AS A RESULT, THE INCIDENCE OF GESTATIONAL DIABETES MELLITUS IS ALSO ON THE RISE. WHILE DIET AND LIFESTYLE CONTRIBUTE TO THESE TRENDS, POPULATION HEALTH DATA SHOW THAT MATERNAL OBESITY AND DIABETES DURING PREGNANCY DURING CRITICAL STAGES OF DEVELOPMENT ARE MAJOR FACTORS THAT CONTRIBUTE TO THE DEVELOPMENT OF CHRONIC DISEASE IN ADOLESCENT AND ADULT OFFSPRING. FETAL PROGRAMMING OF METABOLIC FUNCTION, THROUGH PHYSIOLOGICAL AND (OR) EPIGENETIC MECHANISMS, MAY ALSO HAVE AN INTERGENERATIONAL EFFECT, AND AS A RESULT MAY PERPETUATE METABOLIC DISORDERS IN THE NEXT GENERATION. IN THIS REVIEW, WE SUMMARIZE THE EXISTING LITERATURE THAT CHARACTERIZES HOW MATERNAL OBESITY AND GESTATIONAL DIABETES MELLITUS CONTRIBUTE TO METABOLIC AND CARDIOVASCULAR DISORDERS IN THE OFFSPRING. IN PARTICULAR, WE FOCUS ON ANIMAL STUDIES THAT INVESTIGATE THE MOLECULAR MECHANISMS THAT ARE PROGRAMMED BY THE GESTATIONAL ENVIRONMENT AND LEAD TO DISEASE PHENOTYPES IN THE OFFSPRING. WE ALSO REVIEW INTERVENTIONAL STUDIES THAT PREVENT DISEASE WITH A DEVELOPMENTAL ORIGIN IN THE OFFSPRING. 2015 8 6819 35 [FETAL PROGRAMMING OF METABOLIC DISORDERS]. OUR KNOWLEDGE OF FETAL PROGRAMMING HAS DEVELOPED NOTABLY OVER THE YEARS AND RECENT DATA SUGGEST THAT AN UNBALANCED DIET PRIOR AND DURING PREGNANCY CAN HAVE EARLY-ONSET AND LONG-LASTING CONSEQUENCES ON THE HEALTH OF THE OFFSPRING. SPECIFIC NEGATIVE INFLUENCES OF HIGH DIETARY GLUCOSE AND LIPID CONSUMPTION, AS WELL AS UNDERNUTRITION, ARE ASSOCIATED WITH DEVELOPMENT OF METABOLIC SYNDROME, INSULIN RESISTANCE AND DIABETES IN THE OFFSPRING. THE MECHANISMS UNDERLYING THE EFFECTS OF MATERNAL HYPERGLYCEMIA ON THE FETUS MAY INVOLVE STRUCTURAL, METABOLIC AND EPIGENETIC CHANGES. THE AIM OF THIS REVIEW IS TO ILLUSTRATE HOW ADVERSE INTRAUTERINE ENVIRONMENT MAY INFLUENCE MOLECULAR MODIFICATIONS IN THE FETUS AND CAUSE EPIGENETIC ALTERATIONS IN PARTICULAR. IT HAS BEEN DEMONSTRATED THAT PRENATAL EPIGENETIC MODIFICATIONS MAY BE LINKED TO THE PATHOGENESIS AND PROGRESSION OF THE ADULT CHRONIC DISORDERS. STUDIES ON EPIGENETIC ALTERATIONS WILL CONTRIBUTE TO A BETTER UNDERSTANDING OF THE LONG-TERM EFFECTS OF IN UTERO EXPOSURE AND MAY OPEN NEW PERSPECTIVES FOR DISEASE PREVENTION AND TREATMENT. 2015 9 2038 25 EPIGENETIC CHANGES PREDISPOSING TO TYPE 2 DIABETES IN INTRAUTERINE GROWTH RETARDATION. EPIDEMIOLOGIC STUDIES HAVE DEMONSTRATED AN ASSOCIATION BETWEEN INTRAUTERINE GROWTH RETARDATION AND A GREATER RISK OF CHRONIC DISEASE, INCLUDING CORONARY HEART DISEASE, HYPERTENSION, STROKE, AND TYPE 2 DIABETES IN ADULTHOOD. AN ADVERSE INTRAUTERINE ENVIRONMENT MAY AFFECT BOTH GROWTH AND DEVELOPMENT OF THE ORGANISM, PERMANENTLY PROGRAMMING ENDOCRINE AND METABOLIC FUNCTIONS. ONE OF THE MECHANISMS OF PROGRAMMING IS THE EPIGENETIC MODIFICATION OF GENE PROMOTERS INVOLVED IN THE CONTROL OF KEY METABOLIC PATHWAYS. THE AIM OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF THE EXPERIMENTAL EVIDENCE SHOWING THE EFFECTS OF EARLY EXPOSURE TO SUBOPTIMAL ENVIRONMENT ON EPIGENOME. THE KNOWLEDGE OF THE EPIGENETIC MARKERS OF PROGRAMMING MAY ALLOW THE IDENTIFICATION OF SUSCEPTIBLE INDIVIDUALS AND THE DESIGN OF TARGETED PREVENTION STRATEGIES. 2010 10 4802 32 OBESITY AND LIFESPAN HEALTH--IMPORTANCE OF THE FETAL ENVIRONMENT. A MARKED INCREASE IN THE FREQUENCY OF OBESITY AT THE POPULATION LEVEL HAS RESULTED IN AN INCREASING NUMBER OF OBESE WOMEN ENTERING PREGNANCY. THE INCREASING REALIZATION OF THE IMPORTANCE OF THE FETAL ENVIRONMENT IN RELATION TO CHRONIC DISEASE ACROSS THE LIFESPAN HAS FOCUSED ATTENTION ON THE ROLE OF MATERNAL OBESITY IN FETAL DEVELOPMENT. PREVIOUS STUDIES HAVE DEMONSTRATED THAT OBESITY DURING ADOLESCENCE AND ADULTHOOD CAN BE TRACED BACK TO FETAL AND EARLY CHILDHOOD EXPOSURES. THIS REVIEW FOCUSES ON FACTORS THAT CONTRIBUTE TO EARLY DEVELOPMENTAL EVENTS, SUCH AS EPIGENETIC MODIFICATIONS, THE POTENTIAL FOR AN INCREASE IN INFLAMMATORY BURDEN, EARLY DEVELOPMENTAL PROGRAMMING CHANGES SUCH AS THE VARIABLE DEVELOPMENT OF WHITE VERSUS BROWN ADIPOSE TISSUE, AND ALTERATIONS IN ORGAN ONTOGENY. WE HYPOTHESIZE THAT THESE MECHANISMS PROMOTE AN UNFAVORABLE FETAL ENVIRONMENT AND CAN HAVE A LONG-STANDING IMPACT, WITH EARLY MANIFESTATIONS OF CHRONIC DISEASE THAT CAN RESULT IN AN INCREASED DEMAND FOR FUTURE HEALTH CARE. IN ORDER TO IDENTIFY APPROPRIATE PREVENTIVE MEASURES, ATTENTION NEEDS TO BE PLACED BOTH ON REDUCING MATERNAL OBESITY AS WELL AS UNDERSTANDING THE MOLECULAR, CELLULAR, AND EPIGENETIC MECHANISMS THAT MAY BE RESPONSIBLE FOR THE PRENATAL ONSET OF CHRONIC DISEASE. 2014 11 140 36 ABERRANT DNA METHYLATION MEDIATES THE TRANSGENERATIONAL RISK OF METABOLIC AND CHRONIC DISEASE DUE TO MATERNAL OBESITY AND OVERNUTRITION. MATERNAL OBESITY IS A RAPIDLY EVOLVING UNIVERSAL EPIDEMIC LEADING TO ACUTE AND LONG-TERM MEDICAL AND OBSTETRIC HEALTH ISSUES, INCLUDING INCREASED MATERNAL RISKS OF GESTATIONAL DIABETES, HYPERTENSION AND PRE-ECLAMPSIA, AND THE FUTURE RISKS FOR OFFSPRING'S PREDISPOSITION TO METABOLIC DISEASES. EPIGENETIC MODIFICATION, IN PARTICULAR DNA METHYLATION, REPRESENTS A MECHANISM WHEREBY ENVIRONMENTAL EFFECTS IMPACT ON THE PHENOTYPIC EXPRESSION OF HUMAN DISEASE. MATERNAL OBESITY OR OVERNUTRITION CONTRIBUTES TO THE ALTERATIONS IN DNA METHYLATION DURING EARLY LIFE WHICH, THROUGH FETAL PROGRAMMING, CAN PREDISPOSE THE OFFSPRING TO MANY METABOLIC AND CHRONIC DISEASES, SUCH AS NON-ALCOHOLIC FATTY LIVER DISEASE, OBESITY, DIABETES, AND CHRONIC KIDNEY DISEASE. THIS REVIEW AIMS TO SUMMARIZE FINDINGS FROM HUMAN AND ANIMAL STUDIES, WHICH SUPPORT THE ROLE OF MATERNAL OBESITY IN FETAL PROGRAMING AND THE POTENTIAL BENEFIT OF ALTERING DNA METHYLATION TO LIMIT MATERNAL OBESITY RELATED DISEASE IN THE OFFSPRING. 2021 12 2183 40 EPIGENETIC MECHANISMS RESPONSIBLE FOR THE TRANSGENERATIONAL INHERITANCE OF INTRAUTERINE GROWTH RESTRICTION PHENOTYPES. A POORLY FUNCTIONING PLACENTA RESULTS IN IMPAIRED EXCHANGES OF OXYGEN, NUTRITION, WASTES AND HORMONES BETWEEN THE MOTHER AND HER FETUS. THIS CAN LEAD TO RESTRICTION OF FETAL GROWTH. THESE GROWTH RESTRICTED BABIES ARE AT INCREASED RISK OF DEVELOPING CHRONIC DISEASES, SUCH AS TYPE-2 DIABETES, HYPERTENSION, AND KIDNEY DISEASE, LATER IN LIFE. ANIMAL STUDIES HAVE SHOWN THAT GROWTH RESTRICTED PHENOTYPES ARE SEX-DEPENDENT AND CAN BE TRANSMITTED TO SUBSEQUENT GENERATIONS THROUGH BOTH THE PATERNAL AND MATERNAL LINEAGES. ALTERED EPIGENETIC MECHANISMS, SPECIFICALLY CHANGES IN DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNAS THAT REGULATE EXPRESSION OF GENES THAT ARE IMPORTANT FOR FETAL DEVELOPMENT HAVE BEEN SHOWN TO BE ASSOCIATED WITH THE TRANSMISSION PATTERN OF GROWTH RESTRICTED PHENOTYPES. THIS REVIEW WILL DISCUSS THE SUBSEQUENT HEALTH OUTCOMES IN THE OFFSPRING AFTER GROWTH RESTRICTION AND THE TRANSMISSION PATTERNS OF THESE DISEASES. EVIDENCE OF ALTERED EPIGENETIC MECHANISMS IN ASSOCIATION WITH FETAL GROWTH RESTRICTION WILL ALSO BE REVIEWED. 2022 13 4087 29 MATERNAL OBESITY INCREASES THE RISK OF METABOLIC DISEASE AND IMPACTS RENAL HEALTH IN OFFSPRING. OBESITY, TOGETHER WITH INSULIN RESISTANCE, PROMOTES MULTIPLE METABOLIC ABNORMALITIES AND IS STRONGLY ASSOCIATED WITH AN INCREASED RISK OF CHRONIC DISEASE INCLUDING TYPE 2 DIABETES (T2D), HYPERTENSION, CARDIOVASCULAR DISEASE, NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND CHRONIC KIDNEY DISEASE (CKD). THE INCIDENCE OF OBESITY CONTINUES TO RISE IN ASTRONOMICAL PROPORTIONS THROUGHOUT THE WORLD AND AFFECTS ALL THE DIFFERENT STAGES OF THE LIFESPAN. IMPORTANTLY, THE PROPORTION OF WOMEN OF REPRODUCTIVE AGE WHO ARE OVERWEIGHT OR OBESE IS INCREASING AT AN ALARMING RATE AND HAS POTENTIAL RAMIFICATIONS FOR OFFSPRING HEALTH AND DISEASE RISK. EVIDENCE SUGGESTS A STRONG LINK BETWEEN THE INTRAUTERINE ENVIRONMENT AND DISEASE PROGRAMMING. THE CURRENT REVIEW WILL DESCRIBE THE IMPORTANCE OF THE INTRAUTERINE ENVIRONMENT IN THE DEVELOPMENT OF METABOLIC DISEASE, INCLUDING KIDNEY DISEASE. IT WILL DETAIL THE KNOWN MECHANISMS OF FETAL PROGRAMMING, INCLUDING THE ROLE OF EPIGENETIC MODULATION. THE EVIDENCE FOR THE ROLE OF MATERNAL OBESITY IN THE DEVELOPMENTAL PROGRAMMING OF CKD IS DERIVED MOSTLY FROM OUR RODENT MODELS WHICH WILL BE DESCRIBED. THE CLINICAL IMPLICATION OF SUCH FINDINGS WILL ALSO BE DISCUSSED. 2018 14 4078 36 MATERNAL INFLAMMATION, GROWTH RETARDATION, AND PRETERM BIRTH: INSIGHTS INTO ADULT CARDIOVASCULAR DISEASE. THE "FETAL ORIGIN OF ADULT DISEASE HYPOTHESIS" ORIGINALLY DESCRIBED BY BARKER ET AL. IDENTIFIED THE RELATIONSHIP BETWEEN IMPAIRED IN UTERO GROWTH AND ADULT CARDIOVASCULAR DISEASE RISK AND DEATH. SINCE THEN, NUMEROUS CLINICAL AND EXPERIMENTAL STUDIES HAVE CONFIRMED THAT EARLY DEVELOPMENTAL INFLUENCES CAN LEAD TO CARDIOVASCULAR, PULMONARY, METABOLIC, AND PSYCHOLOGICAL DISEASES DURING ADULTHOOD WITH AND WITHOUT ALTERATIONS IN BIRTH WEIGHT. THIS SO CALLED "FETAL PROGRAMMING" INCLUDES DEVELOPMENTAL DISRUPTION, IMMEDIATE ADAPTATION, OR PREDICTIVE ADAPTATION AND CAN LEAD TO EPIGENETIC CHANGES AFFECTING A SPECIFIC ORGAN OR OVERALL HEALTH. THE INTRAUTERINE ENVIRONMENT IS DRAMATICALLY IMPACTED BY THE OVERALL MATERNAL HEALTH. BOTH PREMATURE BIRTH OR LOW BIRTH WEIGHT CAN RESULT FROM A VARIETY OF MATERNAL CONDITIONS INCLUDING UNDERNUTRITION OR DYSNUTRITION, METABOLIC DISEASES, CHRONIC MATERNAL STRESSES INDUCED BY INFECTIONS AND INFLAMMATION, AS WELL AS HYPERCHOLESTEROLEMIA AND SMOKING. NUMEROUS ANIMAL STUDIES HAVE SUPPORTED THE IMPORTANCE OF BOTH MATERNAL HEALTH AND MATERNAL ENVIRONMENT ON THE LONG TERM OUTCOMES OF THE OFFSPRING. WITH INCREASING RATES OF OBESITY AND DIABETES AND SURVIVAL OF PRETERM INFANTS BORN AT EARLY GESTATIONAL AGES, THE NEED TO ELUCIDATE MECHANISMS RESPONSIBLE FOR PROGRAMMING OF ADULT CARDIOVASCULAR DISEASE IS ESSENTIAL FOR THE TREATMENT OF UPCOMING GENERATIONS. 2011 15 3573 35 IMPACT OF MATERNAL UNDERNUTRITION ON DIABETES AND CARDIOVASCULAR DISEASE RISK IN ADULT OFFSPRING. EPIDEMIOLOGICAL, CLINICAL, AND EXPERIMENTAL OBSERVATIONS HAVE LED TO THE HYPOTHESIS THAT THE RISK OF DEVELOPING CHRONIC DISEASES IN ADULTHOOD IS INFLUENCED NOT ONLY BY GENETIC AND ADULT LIFESTYLE FACTORS, BUT ALSO BY ENVIRONMENTAL FACTORS DURING EARLY LIFE. LOW BIRTH WEIGHT, A MARKER OF INTRAUTERINE STRESS, HAS BEEN LINKED TO PREDISPOSITION TO CARDIOVASCULAR DISEASE (CVD) AND DIABETES. THE COMPELLING ANIMAL EVIDENCE AND SIGNIFICANT HUMAN DATA TO SUPPORT THIS CONCLUSION ARE REVIEWED. SPECIFICALLY, THE REVIEW DISCUSSES THE ROLE OF MATERNAL NUTRITION BEFORE AND DURING PREGNANCY, PLACENTAL INSUFFICIENCIES AND EPIGENETIC CHANGES IN THE INCREASED PREDISPOSITION TO DIABETES AND CVD IN ADULT LIFE. THE IMPACT OF LOW BIRTH WEIGHT AND CATCH-UP GROWTH AS THEY PERTAIN TO RISK OF DISEASE IN ADULT LIFE IS ALSO DISCUSSED. IN ADDITION, ADULT DISEASE RISK IN THE OVERNOURISHED FETUS IS ALSO MENTIONED. REFERENCE IS MADE TO SOME OF THE MECHANISMS OF THE INDUCTION OF DIABETES AND CVD PHENOTYPE. IT IS PROPOSED THAT FETAL NUTRITION, GROWTH AND DEVELOPMENT THROUGH EFFICIENT MATERNAL NUTRITION BEFORE AND DURING PREGNANCY COULD CONSTITUTE THE BASIS FOR NUTRITIONAL STRATEGIES FOR THE PRIMARY PREVENTION OF DIABETES AND CVD. 2009 16 1098 25 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 17 6873 34 [PREVENTION OF OBESITY FROM PERINATAL STAGE]. OBESITY IS ONE OF THE MAJOR HEALTH PROBLEMS AND A DETERMINING FACTOR IN THE PREVALENCE OF DISEASES SUCH AS METABOLIC SYNDROME, ASTHMA, SLEEP APNEA, INFERTILITY AND VARIOUS TYPES OF CANCER. ITS ORIGIN IS MULTIFACTORIAL, INVOLVING GENETIC, SOCIOECONOMIC AND ENVIRONMENTAL FACTORS. THESE LAST ONES CONTRIBUTE MOSTLY TO EXPLAIN THE CURRENT EPIDEMIC GROWTH OF THIS DISEASE. THE SEDENTARY LIFESTYLE, INADEQUATE DIET, LACK OF SLEEP, ALTERATIONS IN INTESTINAL MICROBIOTA AND STRESS ARE FACTORS RELATED TO ITS DEVELOPMENT. SINCE BARKER PRESENTED HIS HYPOTHESIS ABOUT THE "FETAL ORIGIN OF ADULT DISEASES", THERE ARE INCREASING NUMBER OF STUDIES THAT SHOW THE INFLUENCE OF AN INADEQUATE NUTRITIONAL STATUS AND MATERNAL WEIGHT IN THE DEVELOPMENT OF CHRONIC DISEASES, AS OBESITY IN OFFSPRING. THE NUTRITIONAL DEFICIENCIES OF THE PREGNANT MOTHER CAUSE EPIGENETIC MODIFICATIONS AND ABNORMAL PROGRAMMING OF THE DEVELOPMENT OFORGANS AND DEVICES, ADAPTING THE FETUS TO THIS SITUATION OF DEFICIENCY AND BEING ABLE TO ADAPT TO AN OBESOGENIC ENVIRONMENT AFTER BIRTH, INCREASING ITS PROPENSITY TO OBESITY. ALSO, POOR MATERNAL NUTRITIONAL STATUS IS RELATED TO INTRAUTERINE GROWTH RETARDATION AND LOW BIRTH WEIGHT INFANTS, WITH A HIGHER RISK OF CHILDHOOD AND ADULT CENTRAL OBESITY. CURRENTLY, DEFICIENT INTAKE OF MICRONUTRIENTS AND OVERWEIGHT OR MATERNAL OBESITY TEND TO OVERLAP, AND THIS COMBINATION MAY EXACERBATE THE INCREASE IN OBESITY IN THE OFFSPRING. IT IS IMPORTANT TO IDENTIFY PREGNANT MOTHERS AT RISK OF SUFFERING NUTRITIONAL ALTERATIONS AND ESTABLISH THEIR IMPROVEMENT AS A PRIMARY PREVENTION STRATEGY FOR OVERWEIGHT AND OBESITY. 2017 18 5680 30 SHORT- AND LONG-TERM OUTCOMES OF PREECLAMPSIA IN OFFSPRING: REVIEW OF THE LITERATURE. PREECLAMPSIA IS A MULTISYSTEMIC CLINICAL SYNDROME CHARACTERIZED BY THE APPEARANCE OF NEW-ONSET HYPERTENSION AND PROTEINURIA OR HYPERTENSION AND END ORGAN DYSFUNCTION EVEN WITHOUT PROTEINURIA AFTER 20 WEEKS OF PREGNANCY OR POSTPARTUM. RESIDING AT THE SEVERE END OF THE SPECTRUM OF THE HYPERTENSIVE DISORDERS OF PREGNANCY, PREECLAMPSIA OCCURS IN 3 TO 8% OF PREGNANCIES WORLDWIDE AND IS A MAJOR CAUSE OF MATERNAL AND PERINATAL MORBIDITY AND MORTALITY, ACCOUNTING FOR 8-10% OF ALL PRETERM BIRTHS. THE MECHANISM WHEREBY PREECLAMPSIA INCREASES THE RISK OF THE NEURODEVELOPMENTAL, CARDIOVASCULAR, AND METABOLIC MORBIDITY OF THE MOTHER'S OFFSPRING IS NOT WELL KNOWN, BUT IT IS POSSIBLE THAT THE PREECLAMPTIC ENVIRONMENT INDUCES EPIGENETIC CHANGES THAT ADVERSELY AFFECT DEVELOPMENTAL PLASTICITY. THESE DEVELOPMENTAL CHANGES ARE CRUCIAL FOR OPTIMAL FETAL GROWTH AND SURVIVAL BUT MAY LEAD TO AN INCREASED RISK OF CHRONIC MORBIDITY IN CHILDHOOD AND EVEN LATER IN LIFE. THE AIM OF THIS REVIEW IS TO SUMMARIZE BOTH THE SHORT- AND LONG-TERM EFFECTS OF PREECLAMPSIA ON OFFSPRING BASED ON THE CURRENT LITERATURE. 2023 19 5647 43 SEX DIFFERENCES IN FETAL KIDNEY REPROGRAMMING: THE CASE IN THE RENIN-ANGIOTENSIN SYSTEM. DURING THE EARLY STAGES OF THE DEVELOPMENT OF THE LIVING MULTIORGAN SYSTEMS, GENOME MODIFICATIONS OTHER THAN SEQUENCE VARIATION OCCUR THAT GUIDE CELL DIFFERENTIATION AND ORGANOGENESIS. THESE MODIFICATIONS ARE KNOWN TO OPERATE AS A FETAL PROGRAMMING CODE DURING THIS PERIOD, AND RECENT RESEARCH INDICATES THAT THERE ARE SOME TISSUE-SPECIFIC CODES IN ORGANOGENESIS WHOSE EFFECTS MAY PERSIST AFTER BIRTH UNTIL ADULTHOOD. CONSEQUENTLY, THE EVENTS THAT DISRUPT THE PRE-ESTABLISHED EPIGENETIC PATTERN COULD INDUCE SHIFTS IN ORGAN PHYSIOLOGY, WITH IMPLICATIONS ON HEALTH FROM BIRTH OR LATER IN ADULT LIFE. CHRONIC KIDNEY DISEASE (CKD) IS ONE OF THE MAIN CAUSES OF MORTALITY WORLDWIDE; ITS ETIOLOGY IS MULTIFACTORIAL, BUT DIABETES, OBESITY, AND HYPERTENSION ARE THE MAIN CAUSES OF CKD IN ADULTS, ALTHOUGH THERE ARE OTHER RISK FACTORS THAT ARE MAINLY ASSOCIATED WITH AN INDIVIDUAL'S LIFESTYLE. RECENT STUDIES SUGGEST THAT FETAL REPROGRAMMING IN THE DEVELOPING KIDNEY COULD BE IMPLICATED IN THE SUSCEPTIBILITY TO KIDNEY DISEASE IN BOTH CHILDHOOD AND ADULTHOOD. SOME EPIGENETIC MODIFICATIONS, SUCH AS GENOME METHYLATION STATUS, DYSREGULATION OF MIRNA, AND HISTONE CODING ALTERATIONS IN GENES RELATED TO THE REGULATION OF THE RENIN-ANGIOTENSIN AXIS, A COMMON DENOMINATOR IN CKD, MAY HAVE ORIGINATED DURING FETAL DEVELOPMENT. THIS REVIEW FOCUSES ON EPIGENETIC CHANGES DURING NEPHROGENESIS AND THEIR REPERCUSSIONS ON KIDNEY HEALTH AND DISEASE. IN ADDITION, THE FOCUS IS ON THE INFLUENCE OF ENVIRONMENTAL FACTORS DURING PREGNANCY, SUCH AS MATERNAL METABOLIC DISEASES AND DIETARY AND METABOLIC CONDITIONS, AS WELL AS SOME SEX DIFFERENCES IN FETAL KIDNEY REPROGRAMMING DURING WHICH DYSREGULATION OF THE RENIN-ANGIOTENSIN SYSTEM IS INVOLVED. 2023 20 48 37 A CRUCIAL ROLE FOR MATERNAL DIETARY METHYL DONOR INTAKE IN EPIGENETIC PROGRAMMING AND FETAL GROWTH OUTCOMES. THE FETAL ORIGINS OF HEALTH AND DISEASE FRAMEWORK HAS IDENTIFIED EXTREMES IN FETAL GROWTH AND BIRTH WEIGHT AS FACTORS ASSOCIATED WITH THE LIFELONG GENERATION OF CHRONIC DISEASES SUCH AS OBESITY, DIABETES, CARDIOVASCULAR DISEASE, AND HYPERTENSION. MATERNAL NUTRITION PLAYS A CRITICAL ROLE IN FETAL AND PLACENTAL DEVELOPMENT, IN PART BY PROVIDING THE METHYL GROUPS REQUIRED TO ESTABLISH THE FETUS'S GENOME STRUCTURE AND FUNCTION, NOTABLY THROUGH DNA METHYLATION. THE GOAL OF THIS NARRATIVE REVIEW IS TO DESCRIBE THE ROLE OF MATERNAL DIETARY METHYL DONOR (METHIONINE, FOLATE, AND CHOLINE) AND COFACTOR (ZINC AND VITAMINS B2, B6, AND B12) INTAKE IN ONE-CARBON METABOLISM AND DNA METHYLATION IN THE FETUS AND PLACENTA, AS WELL AS THEIR IMPACTS ON FETAL GROWTH AND LIFELONG HEALTH OUTCOMES, WITH SPECIFIC EXAMPLES IN ANIMALS AND HUMANS. BASED ON THE AVAILABLE EVIDENCE, IT IS CONCLUDED THAT INTAKE OF DIFFERENT AMOUNTS OF DIETARY METHYL DONORS AND COFACTORS DURING PREGNANCY MAY ALTER FETAL GROWTH AND DEVELOPMENT, THUS ESTABLISHING A MAJOR LINK BETWEEN EARLY ENVIRONMENTAL EXPOSURE AND DISEASE DEVELOPMENT IN THE OFFSPRING LATER IN LIFE. 2018