1 1375 114 DEVELOPMENTAL PROGRAMMING OF ADULT HAEMATOPOIESIS SYSTEM. THE BARKER HYPOTHESIS OF 'FOETAL ORIGIN OF ADULT DISEASES' HAS LED TO EMPHASIZE THE CONCEPT OF 'DEVELOPMENTAL PROGRAMMING', BASED ON THE CRUCIAL ROLE OF EPIGENETIC FACTORS. ACCORDINGLY, IT HAS BEEN DEMONSTRATED THAT PARENTAL ADVERSITY (BEFORE CONCEPTION AND DURING PREGNANCY) AND FOETAL FACTORS (I.E., HYPOXIA, MALNUTRITION AND PLACENTAL INSUFFICIENCY) PERMANENTLY MODIFY THE PHYSIOLOGICAL SYSTEMS OF THE PROGENY, PREDISPOSING THEM TO PREMATURE AGEING AND CHRONIC DISEASE DURING ADULTHOOD. THUS, AN ALTERED FUNCTIONALITY OF THE ENDOCRINE, IMMUNE, NERVOUS AND CARDIOVASCULAR SYSTEMS IS OBSERVED IN THE PROGENY. HOWEVER, IT REMAINS TO BE UNDERSTOOD WHETHER THE HAEMATOPOIETIC SYSTEM ITSELF ALSO REPRESENTS A PORTRAIT OF FOETAL PROGRAMMING. HERE, WE PROVIDE EVIDENCE, REPORTING AND DISCUSSING RELATED THEORIES, AND RESULTS OF STUDIES DESCRIBED IN THE LITERATURE. IN ADDITION, WE HAVE OUTLINED OUR OPINIONS AND SUGGEST HOW IT IS POSSIBLE TO INTERVENE TO CORRECT FOETAL MAL-PROGRAMMING. SOME PRO-HEALTH INTERVENTIONS AND RECOMMENDATIONS ARE PROPOSED, WITH THE HOPE OF GUARANTEE THE HEALTH OF FUTURE GENERATIONS AND TRYING TO COMBAT THE CONTINUOUS INCREASE IN AGE-RELATED DISEASES IN HUMAN POPULATIONS. 2019 2 4189 26 METABOLIC DISEASE PROGRAMMING: FROM MITOCHONDRIA TO EPIGENETICS, GLUCOCORTICOID SIGNALLING AND BEYOND. EMBRYONIC AND FOETAL DEVELOPMENT ARE CRITICAL PERIODS OF DEVELOPMENT IN WHICH SEVERAL ENVIRONMENTAL CUES DETERMINE HEALTH AND DISEASE IN ADULTHOOD. MATERNAL CONDITIONS AND AN UNFAVOURABLE INTRAUTERINE ENVIRONMENT IMPACT FOETAL DEVELOPMENT AND MAY PROGRAMME THE OFFSPRING FOR INCREASED PREDISPOSITION TO METABOLIC DISEASES AND OTHER CHRONIC PATHOLOGIC CONDITIONS THROUGHOUT ADULT LIFE. PREVIOUSLY, NON-COMMUNICABLE CHRONIC DISEASES WERE ONLY ASSOCIATED WITH GENETICS AND LIFESTYLE. NOW THE ORIGINS OF NON-COMMUNICABLE CHRONIC DISEASES ARE ASSOCIATED WITH EARLY-LIFE ADAPTATIONS THAT PRODUCE LONG-TERM DYSFUNCTION. EARLY-LIFE ENVIRONMENT SETS THE LONG-TERM HEALTH AND DISEASE RISK AND CAN SPAN THROUGH MULTIPLE GENERATIONS. RECENT RESEARCH IN DEVELOPMENTAL PROGRAMMING AIMS AT IDENTIFYING THE MOLECULAR MECHANISMS RESPONSIBLE FOR DEVELOPMENTAL PROGRAMMING OUTCOMES THAT IMPACT CELLULAR PHYSIOLOGY AND TRIGGER ADULTHOOD DISEASE. THE IDENTIFICATION OF NEW THERAPEUTIC TARGETS CAN IMPROVE OFFSPRING'S HEALTH MANAGEMENT AND PREVENT OR OVERCOME ADVERSE CONSEQUENCES OF FOETAL PROGRAMMING. THIS REVIEW SUMMARIZES RECENT BIOMEDICAL DISCOVERIES IN THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) HYPOTHESIS AND HIGHLIGHT POSSIBLE DEVELOPMENTAL PROGRAMMING MECHANISMS, INCLUDING PRENATAL STRUCTURAL DEFECTS, METABOLIC (MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, PROTEIN MODIFICATION), EPIGENETIC AND GLUCOCORTICOID SIGNALLING-RELATED MECHANISMS SUGGESTING MOLECULAR CLUES FOR THE CAUSES AND CONSEQUENCES OF PROGRAMMING OF INCREASED SUSCEPTIBILITY OF OFFSPRING TO METABOLIC DISEASE AFTER BIRTH. IDENTIFYING MECHANISMS INVOLVED IN DOHAD CAN CONTRIBUTE TO EARLY INTERVENTIONS IN PREGNANCY OR EARLY CHILDHOOD, TO RE-SET THE METABOLIC HOMEOSTASIS AND BREAK THE CHAIN OF SUBSEQUENT EVENTS THAT COULD LEAD TO THE DEVELOPMENT OF DISEASE. 2021 3 1766 32 EARLY-LIFE EXPERIENCES AND THE DEVELOPMENT OF ADULT DISEASES WITH A FOCUS ON MENTAL ILLNESS: THE HUMAN BIRTH THEORY. IN MAMMALS, EARLY ADVERSE EXPERIENCES, INCLUDING MOTHER-PUP INTERACTIONS, SHAPE THE RESPONSE OF AN INDIVIDUAL TO CHRONIC STRESS OR TO STRESS-RELATED DISEASES DURING ADULT LIFE. THIS HAS LED TO THE ELABORATION OF THE THEORY OF THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, IN PARTICULAR ADULT DISEASES SUCH AS CARDIOVASCULAR AND METABOLIC DISORDERS. IN ADDITION, IN HUMANS, AS STATED BY MASSIMO FAGIOLI'S HUMAN BIRTH THEORY, BIRTH IS HEALTHY AND EQUAL FOR ALL INDIVIDUALS, SO THAT MENTAL ILLNESS DEVELOP EXCLUSIVELY IN THE POSTNATAL PERIOD BECAUSE OF THE QUALITY OF THE RELATIONSHIP IN THE FIRST YEAR OF LIFE. THUS, THIS REVIEW FOCUSES ON THE IMPORTANCE OF PROGRAMMING DURING THE EARLY DEVELOPMENTAL PERIOD ON THE MANIFESTATION OF ADULT DISEASES IN BOTH ANIMAL MODELS AND HUMANS. CONSIDERING THE OBVIOUS DIFFERENCES BETWEEN ANIMALS AND HUMANS WE CANNOT SYSTEMATICALLY MOVE FROM ANIMAL MODELS TO HUMANS. CONSEQUENTLY, IN THE FIRST PART OF THIS REVIEW, WE WILL DISCUSS HOW ANIMAL MODELS CAN BE USED TO DISSECT THE INFLUENCE OF ADVERSE EVENTS OCCURRING DURING THE PRENATAL AND POSTNATAL PERIODS ON THE DEVELOPMENTAL TRAJECTORIES OF THE OFFSPRING, AND IN THE SECOND PART, WE WILL DISCUSS THE ROLE OF POSTNATAL CRITICAL PERIODS ON THE DEVELOPMENT OF MENTAL DISEASES IN HUMANS. EPIGENETIC MECHANISMS THAT CAUSE REVERSIBLE MODIFICATIONS IN GENE EXPRESSION, DRIVING THE DEVELOPMENT OF A PATHOLOGICAL PHENOTYPE IN RESPONSE TO A NEGATIVE EARLY POSTNATAL ENVIRONMENT, MAY LIE AT THE CORE OF THIS PROGRAMMING, THEREBY PROVIDING POTENTIAL NEW THERAPEUTIC TARGETS. THE CONCEPT OF THE HUMAN BIRTH THEORY LEADS TO A COMPREHENSION OF THE MENTAL ILLNESS AS A PATHOLOGY OF THE HUMAN RELATIONSHIP IMMEDIATELY AFTER BIRTH AND DURING THE FIRST YEAR OF LIFE. 2017 4 1992 29 EPIGENETIC AND DEVELOPMENTAL INFLUENCES ON THE RISK OF OBESITY, DIABETES, AND METABOLIC SYNDROME. METABOLIC SYNDROME IS A GROWING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. METABOLIC SYNDROME IS CHARACTERIZED BY THE PRESENCE OF A VARIETY OF METABOLIC DISTURBANCES INCLUDING OBESITY, HYPERLIPIDEMIA, HYPERTENSION, AND ELEVATED FASTING BLOOD SUGAR. ALTHOUGH THE RISK FOR METABOLIC SYNDROME HAS LARGELY BEEN ATTRIBUTED TO ADULT LIFESTYLE FACTORS SUCH AS POOR NUTRITION, LACK OF EXERCISE, AND SMOKING, THERE IS NOW STRONG EVIDENCE SUGGESTING THAT PREDISPOSITION TO THE DEVELOPMENT OF METABOLIC SYNDROME BEGINS IN UTERO. FIRST POSITED BY HALES AND BARKER IN 1992, THE "THRIFTY PHENOTYPE" HYPOTHESIS PROPOSES THAT SUSCEPTIBILITY TO ADULT CHRONIC DISEASES CAN OCCUR IN RESPONSE TO EXPOSURES IN THE PRENATAL AND PERINATAL PERIODS. THIS HYPOTHESIS HAS BEEN CONTINUALLY SUPPORTED BY EPIDEMIOLOGIC STUDIES AND STUDIES INVOLVING ANIMAL MODELS. IN THIS REVIEW, WE DESCRIBE THE STRUCTURAL, METABOLIC AND EPIGENETIC CHANGES THAT OCCUR IN RESPONSE TO ADVERSE INTRAUTERINE ENVIRONMENTS INCLUDING PRENATAL AND POSTNATAL DIET, MATERNAL OBESITY, AND PREGNANCY COMPLICATIONS. GIVEN THE INCREASING PREVALENCE OF METABOLIC SYNDROME IN BOTH THE DEVELOPED AND DEVELOPING WORLDS, A GREATER UNDERSTANDING AND APPRECIATION FOR THE ROLE OF THE INTRAUTERINE ENVIRONMENT IN ADULT CHRONIC DISEASE ETIOLOGY IS IMPERATIVE. 2015 5 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 6 6814 25 [EVIDENCE AND MECHANISMS OF FETAL ORIGINS OF ADULT DISEASES]. THIS REVIEW FOCUSES ON THE FETAL ORIGINS OF ADULT DISEASE HYPOTHESIS PUT FORWARD BY DAVID BARKER AND HIS COLLEAGUES, RECENT ADVANCES IN EPIDEMIOLOGICAL STUDIES AND EXPERIMENTAL RESEARCH IN THIS FIELD. BARKER HYPOTHESIS STATES THAT ENVIRONMENTAL FACTORS, PARTICULARLY INTRAUTERINE NUTRITION, AS INDICATED BY BIRTH WEIGHT, OPERATE IN EARLY LIFE TO PROGRAM THE RISKS FOR ADVERSE HEALTH OUTCOMES IN ADULT LIFE. A LARGE GROWING BODY OF REPORTS DESCRIBED THE ASSOCIATION BETWEEN THE EARLY DEVELOPMENT AND ADULT DISEASES, SUCH AS DIABETES, HYPERTENSION, CORONARY HEART DISEASE, ABNORMAL LIPIDS METABOLISM, OBESITY AND CANCER, ETC. EXPERIMENTAL STUDIES SHOW THAT THE CHANGES OF SOME KEY GENES' EXPRESSION, CAUSED BY EPIGENETIC MODIFICATIONS, LEAD TO A PERMANENT ALTERATION OF CELLULAR PROLIFERATION AND DIFFERENTIATION AND FINALLY THE GENESIS IN KEY TISSUES AND ORGANS. THESE RESULTS BRING ABOUT THE IMPAIRMENT IN STRUCTURES AND FUNCTIONS AND THE INCREASED SUSCEPTIBILITY TO CHRONIC DISEASES IN ADULT LIFE. THE HYPOTHESIS PROVIDES A NEW PERSPECTIVE FOR THE PREVENTION AND THERAPY OF CHRONIC DISEASES. 2007 7 6803 23 [EPIGENETIC MECHANISMS IN PHYSIOLOGIC AND PATHOLOGIC PREGNANCIES]. EPIGENETIC FACTORS ARE NOWADAYS IN THE FOCUS OF SCIENTIFIC INTEREST IN MEDICINE INCLUDING OBSTETRICS. THE ENVIRONMENT IN UTERO AND EARLY NEONATAL LIFE MAY INDUCE A PERMANENT RESPONSE IN THE FETUS AND THE NEWBORN LEADING TO ENHANCED SUSCEPTIBILITY TO LATER DISEASES. THERE IS NOW GROWING EVIDENCE THAT THE EFFECTS OF DEVELOPMENTAL PROGRAMMING MAY ALSO MANIFEST THEMSELVES IN THE NEXT GENERATIONS WITHOUT FURTHER SUBOPTIMAL EXPOSURE. THE SO-CALLED FETAL PROGRAMMING MAY ALSO HIGHLIGHT A TIGHT CONNECTION BETWEEN PATHOLOGICAL CONDITIONS IN PREGNANCY, ENVIRONMENTAL FACTORS AND THE DEVELOPMENT OF CHRONIC DISEASES IN ADULTHOOD. INVESTIGATION OF EPIGENETIC FACTORS MAY YIELD NEW POSSIBILITIES FOR THE PREVENTION OF CHRONIC DISEASES AFFECTING A SIGNIFICANT PART OF THE POPULATION. 2014 8 2007 30 EPIGENETIC BASIS FOR FETAL ORIGINS OF AGE-RELATED DISEASE. THE CURRENT CONCEPT OF FETAL ORIGINS OF ADULT DISEASES DESCRIBES IN UTERO PROGRAMMING, OR ADAPTATION TO A SPECTRUM OF ADVERSE ENVIRONMENTAL CONDITIONS THAT ULTIMATELY LEADS TO INCREASED SUSCEPTIBILITY TO AGE-RELATED DISEASES (E.G., TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE) LATER IN LIFE. ALTHOUGH THE PRECISE MECHANISM OF THIS BIOLOGICAL MEMORY REMAINS UNCLEAR, MOUNTING EVIDENCE SUGGESTS AN EPIGENETIC BASIS. THE INCREASED SUSCEPTIBILITY TO CHRONIC DISEASE AND INVOLVEMENT OF MULTIPLE ORGAN SYSTEMS THAT IS OBSERVED IS ANALOGOUS TO THE DECLINE IN RESISTANCE TO DISEASE THAT IS TYPICAL OF NORMAL AGING. ALTHOUGH THE CUMULATIVE ENVIRONMENT OVER THE COURSE OF A LIFETIME CAN INDUCE INCREASING EPIGENETIC DYSREGULATION, WE PROPOSE THAT ADVERSE EVENTS THAT OCCUR DURING EARLY DEVELOPMENT CAN INDUCE SIGNIFICANT ADDITIONAL DYSREGULATION OF THE EPIGENOME. HERE, WE DESCRIBE THE CURRENT EVIDENCE FOR FETAL ORIGINS OF ADULT DISEASE AND THE ASSOCIATED ROLE OF EPIGENETIC DYSREGULATION. IN ADDITION, WE PRESENT A NEW PERSPECTIVE ON THE INDUCTION OF EPIGENETIC ALTERATIONS IN UTERO, WHICH SUBSEQUENTLY LEAD TO AN AGING PHENOTYPE MARKED BY INCREASED SUSCEPTIBILITY TO AGE-RELATED DISEASES. 2010 9 6819 32 [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 10 5247 22 PROGRAMMED ADULT KIDNEY DISEASE: IMPORTANCE OF FETAL ENVIRONMENT. THE BARKER HYPOTHESIS STRONGLY SUPPORTED THE INFLUENCE OF FETAL ENVIRONMENT ON THE DEVELOPMENT OF CHRONIC DISEASES IN LATER LIFE. MULTIPLE EXPERIMENTAL AND HUMAN STUDIES HAVE IDENTIFIED THAT THE DELETERIOUS EFFECT OF FETAL PROGRAMMING COMMONLY LEADS TO ALTERATIONS IN RENAL DEVELOPMENT. THE INTERPLAY BETWEEN ENVIRONMENTAL INSULTS AND FETAL GENOME CAN INDUCE EPIGENETIC CHANGES AND LEAD TO ALTERATIONS IN THE EXPRESSION OF RENAL PHENOTYPE. IN THIS REVIEW, WE HAVE EXPLORED THE RENAL DEVELOPMENT AND ITS FUNCTIONS, WHILE FOCUSING ON THE EPIGENETIC FINDINGS AND FUNCTIONAL ASPECTS OF THE RENIN-ANGIOTENSIN SYSTEM AND ITS COMPONENTS. 2020 11 1922 29 ENVIRONMENTAL EPIGENETIC INTERACTION OF GAMETES AND EARLY EMBRYOSDAGGER. IN RECENT YEARS, THE DEVELOPMENTAL ORIGINS OF DISEASES HAVE BEEN INCREASINGLY RECOGNIZED AND ACCEPTED. AS SUCH, IT HAS BEEN SUGGESTED THAT MOST ADULTHOOD CHRONIC DISEASES SUCH AS DIABETES, OBESITY, CARDIOVASCULAR DISEASE, AND EVEN TUMORS MAY DEVELOP AT A VERY EARLY STAGE. IN ADDITION TO INTRAUTERINE ENVIRONMENTAL EXPOSURE, GERM CELLS CARRY AN IMPORTANT INHERITANCE ROLE AS THE PRIMARY LINK BETWEEN THE TWO GENERATIONS. ADVERSE EXTERNAL INFLUENCES DURING DIFFERENTIATION AND DEVELOPMENT CAN CAUSE DAMAGE TO GERM CELLS, WHICH MAY THEN INCREASE THE RISK OF CHRONIC DISEASE DEVELOPMENT LATER IN LIFE. HERE, WE FURTHER ELUCIDATE AND CLARIFY THE CONCEPT OF GAMETE AND EMBRYO ORIGINS OF ADULT DISEASES BY FOCUSING ON THE ENVIRONMENTAL INSULTS ON GERM CELLS, FROM DIFFERENTIATION TO MATURATION AND FERTILIZATION. 2022 12 1365 36 DEVELOPMENTAL ORIGIN OF CHRONIC DISEASES: TOXICOLOGICAL IMPLICATION. HUMAN EPIDEMIOLOGICAL AND EXPERIMENTAL ANIMAL STUDIES SHOW THAT SUBOPTIMAL ENVIRONMENTS IN FETAL AND NEONATAL LIFE EXERTS A PROFOUND INFLUENCE ON PHYSIOLOGICAL FUNCTION AND RISK OF DISEASE IN ADULT LIFE. THE MOLECULAR, CELLULAR, METABOLIC, ENDOCRINE AND PHYSIOLOGICAL ADAPTATIONS TO INTRAUTERINE NUTRITIONAL CONDITIONS RESULT IN PERMANENT ALTERATIONS OF CELLULAR PROLIFERATION AND DIFFERENTIATION OF TISSUES AND ORGAN SYSTEMS, WHICH IN TURN CAN MANIFEST BY PATHOLOGICAL CONSEQUENCES OR INCREASED VULNERABILITY TO CHRONIC DISEASES IN ADULTHOOD. INTRAUTERINE GROWTH RESTRICTION (IUGR) DUE TO INTRAUTERINE DEVELOPMENT DERANGEMENTS IS CONSIDERED THE IMPORTANT FACTOR IN DEVELOPMENT OF SUCH DISEASES AS ESSENTIAL HYPERTENSION, DIABETES MELLITUS, ISCHEMIC DISEASES OF THE HEART, OSTEOPOROSIS, RESPIRATORY, NEUROPSYCHIATRIC AND IMMUNE SYSTEM DISEASES.AN EARLY LIFE EXPOSURES TO DIETARY AND ENVIRONMENTAL EXPOSURES CAN HAVE A IMPORTANT EFFECT ON EPIGENETIC CODE, RESULTING IN DISEASES DEVELOPED LATER IN LIFE. THE CONCEPT OF THE "DEVELOPMENTAL PROGRAMMING" AND DEVELOPMENTAL ORIGINS OF ADULT DISEASES (DOHAD) HAS BECOME WELL ACCEPTED BECAUSE OF THE COMPELLING ANIMAL STUDIES THAT HAVE PRECISELY DEFINED THE OUTCOMES OF SPECIFIC EXPOSURES.THE ENVIRONMENTAL POLLULLUTANTS AND OTHER CHEMICAL TOXICANTS MAY INFLUENCE CRUCIAL CELLULAR FUNCTIONS DURING CRITICAL PERIODS OF FETAL DEVELOPMENT AND PERMANENTLY ALTER THE STRUCTURE OR FUNCTION OF SPECIFIC ORGAN SYSTEMS. DEVELOPMENTAL EPIGENETICS IS BELIEVED TO ESTABLISH "ADAPTIVE" PHENOTYPES TO MEET THE DEMANDS OF THE LATER-LIFE ENVIRONMENT. RESULTING PHENOTYPES THAT MATCH PREDICTED LATER-LIFE DEMANDS WILL PROMOTE HEALTH, WHILE A HIGH DEGREE OF MISMATCH WILL IMPEDE ADAPTABILITY TO LATER-LIFE CHALLENGES AND ELEVATE DISEASE RISK. THE RAPID INTRODUCTION OF SYNTHETIC CHEMICALS, ENVIRONMENTAL POLLUTANTS AND MEDICAL INTERVENTIONS, MAY RESULT IN CONFLICT WITH THE PROGRAMMED ADAPTIVE CHANGES MADE DURING EARLY DEVELOPMENT, AND EXPLAIN THE ALARMING INCREASES IN SOME DISEASES. 2008 13 6844 27 [METABOLIC PROGRAMMING: THEORETICAL CONCEPTS AND EXPERIMENTAL EVIDENCE]. IT IS KNOWN THAT THE POOR NUTRITION DURING A FETAL DEVELOPMENT MAY CONTRIBUTE TO AN INCREASED RISK OF CHRONIC DISEASES IN ADULTHOOD. IN A MODERN LITERATURE, THIS PHENOMENON IS CALLED <>. IT IS ASSUMED THAT THE QUALITATIVE OR QUANTITATIVE DEFICIENCY OF CERTAIN NUTRITIONAL COMPONENTS DURING AN EARLY DEVELOPMENT MAY LEAD TO THE ADAPTATIONS THAT CONTRIBUTE TO IMPROVED SURVIVAL DURING THE PRENATAL AND EARLY POSTNATAL PERIODS OF AN ONTOGENESIS. HOWEVER, THE CONSEQUENCE OF SUCH ADAPTIVE CHANGES MAY ALSO BE THE DEVELOPMENT OF VARIOUS PATHOLOGICAL PROCESSES AT THE LATER STAGES OF LIFE. RECENT STUDIES HAVE SHOWN THAT ONE OF THE MAJOR MECHANISMS INVOLVED IN THESE ADAPTATIONS IS THE EPIGENETIC REGULATION OF A GENE ACTIVITY. IN THIS REVIEW, THE EXPERIMENTAL EVIDENCE IS PROVIDED THAT PROCESSES ARISING FROM A QUANTITATIVELY OR QUALITATIVELY RESTRICTED DIET DURING THE EARLY STAGES OF DEVELOPMENT PLAY AN IMPORTANT ROLE IN THE FURTHER LIFE AND CAN GREATLY INFLUENCE RISK OF VARIOUS AGE-RELATED DISEASES AND LIFE SPAN. 2013 14 1769 29 EARLY-LIFE NUTRITIONAL PROGRAMMING OF LONGEVITY. AVAILABLE DATA FROM BOTH EXPERIMENTAL AND EPIDEMIOLOGICAL STUDIES SUGGEST THAT INADEQUATE DIET IN EARLY LIFE CAN PERMANENTLY CHANGE THE STRUCTURE AND FUNCTION OF SPECIFIC ORGANS OR HOMOEOSTATIC PATHWAYS, THEREBY 'PROGRAMMING' THE INDIVIDUAL'S HEALTH STATUS AND LONGEVITY. SUFFICIENT EVIDENCE HAS ACCUMULATED SHOWING SIGNIFICANT IMPACT OF EPIGENETIC REGULATION MECHANISMS IN NUTRITIONAL PROGRAMMING PHENOMENON. THE ESSENTIAL ROLE OF EARLY-LIFE DIET IN THE DEVELOPMENT OF AGING-RELATED CHRONIC DISEASES IS WELL ESTABLISHED AND DESCRIBED IN MANY SCIENTIFIC PUBLICATIONS. HOWEVER, THE PROGRAMMING EFFECTS ON LIFESPAN HAVE NOT BEEN EXTENSIVELY REVIEWED SYSTEMATICALLY. THE AIM OF THE REVIEW IS TO PROVIDE A SUMMARY OF RESEARCH FINDINGS AND THEORETICAL EXPLANATIONS THAT INDICATE THAT LONGEVITY CAN BE INFLUENCED BY EARLY NUTRITION. 2014 15 4996 25 PERINATAL EPIGENETIC DETERMINANTS OF COGNITIVE AND METABOLIC DISORDERS. MULTIPLE CUES FROM THE ENVIRONMENT OF OUR INDIRECT AND IMMEDIATE ANCESTORS, WHICH OFTEN PERSIST THROUGHOUT THE PRENATAL PERIOD AND ADULTHOOD, ARE SHAPING OUR PHENOTYPES THROUGH EITHER DIRECT, PARENT-TO-CHILD INFLUENCES, OR TRANSGENERATIONAL INHERITANCE. THESE EFFECTS ARE DUE TO GENE-ENVIRONMENT INTERACTIONS, WHICH ARE INTENDED TO BE A PREDICTIVE TOOL AND A MECHANISM OF QUICK ADAPTATION TO THE ENVIRONMENT, AS COMPARED WITH GENETIC VARIATIONS THAT ARE INHERITED OVER MANY GENERATIONS. IN CERTAIN CIRCUMSTANCES THE INFLUENCES INDUCED BY THE GENE-ENVIRONMENT INTERACTIONS CAN HAVE DELETERIOUS EFFECTS UPON THE HEALTH STATUS, IN THE CONTEXT OF A RADICAL CHANGE IN THE ENVIRONMENT THAT DOES NOT FIT WITH THE PREDICTED CONDITIONS, VIA EPIGENETIC ALTERATIONS. CONVERSELY THE BEST FIT TO THE EXPECTED ENVIRONMENT MIGHT HAVE A DELAYED AGING PROCESS AND A LONGER LIFE SPAN. THIS REVIEW WILL TOUCH UPON THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) CONCEPT, WHILE DISCUSSING RECENT ADVANCES IN THE UNDERSTANDING OF METABOLIC AND COGNITIVE DISRUPTIONS, WITH A FOCUS ON EPIGENETIC FACTORS, THEIR TRANSGENERATIONAL EFFECTS, AND THE CONSEQUENCES THEY MIGHT HAVE UPON THE ONSET OF CHRONIC DISEASE AND PREMATURE EXITUS. 2012 16 2103 29 EPIGENETIC EPIDEMIOLOGY OF THE DEVELOPMENTAL ORIGINS HYPOTHESIS. EXTENSIVE HUMAN EPIDEMIOLOGIC AND ANIMAL MODEL DATA INDICATE THAT DURING CRITICAL PERIODS OF PRENATAL AND POSTNATAL MAMMALIAN DEVELOPMENT, NUTRITION AND OTHER ENVIRONMENTAL STIMULI INFLUENCE DEVELOPMENTAL PATHWAYS AND THEREBY INDUCE PERMANENT CHANGES IN METABOLISM AND CHRONIC DISEASE SUSCEPTIBILITY. THE BIOLOGIC MECHANISMS UNDERLYING THIS "DEVELOPMENTAL ORIGINS HYPOTHESIS" ARE POORLY UNDERSTOOD. THIS REVIEW FOCUSES ON THE LIKELY INVOLVEMENT OF EPIGENETIC MECHANISMS IN THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD). WE DESCRIBE PERMANENT EFFECTS OF TRANSIENT ENVIRONMENTAL INFLUENCES ON THE DEVELOPMENTAL ESTABLISHMENT OF EPIGENETIC GENE REGULATION AND EVIDENCE LINKING EPIGENETIC DYSREGULATION WITH HUMAN DISEASE. WE PROPOSE A DEFINITION OF "EPIGENETIC EPIDEMIOLOGY" AND DELINEATE HOW THIS EMERGING FIELD PROVIDES A BASIS FROM WHICH TO EXPLORE THE ROLE OF EPIGENETIC MECHANISMS IN DOHAD. WE SUGGEST STRATEGIES FOR FUTURE HUMAN EPIDEMIOLOGIC STUDIES TO IDENTIFY CAUSAL ASSOCIATIONS BETWEEN EARLY EXPOSURES, LONG-TERM CHANGES IN EPIGENETIC REGULATION, AND DISEASE, WHICH MAY ULTIMATELY ENABLE SPECIFIC EARLY-LIFE INTERVENTIONS TO IMPROVE HUMAN HEALTH. 2007 17 4782 28 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 18 317 35 ALCOHOL-INDUCED DEVELOPMENTAL ORIGINS OF ADULT-ONSET DISEASES. FETAL ALCOHOL EXPOSURE MAY IMPAIR GROWTH, DEVELOPMENT, AND FUNCTION OF MULTIPLE ORGAN SYSTEMS AND IS ENCOMPASSED BY THE TERM FETAL ALCOHOL SPECTRUM DISORDERS (FASD). RESEARCH HAS SO FAR FOCUSED ON THE MECHANISMS, PREVENTION, AND DIAGNOSIS OF FASD, WHILE THE RISK FOR ADULT-ONSET CHRONIC DISEASES IN INDIVIDUALS EXPOSED TO ALCOHOL IN UTERO IS NOT WELL EXPLORED. DAVID BARKER'S HYPOTHESIS ON DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) SUGGESTS THAT INSULTS TO THE MILIEU OF THE DEVELOPING FETUS PROGRAM IT FOR ADULT DEVELOPMENT OF CHRONIC DISEASES. IN THE 25 YEARS SINCE THE INTRODUCTION OF THIS HYPOTHESIS, EPIDEMIOLOGICAL AND ANIMAL MODEL STUDIES HAVE MADE SIGNIFICANT ADVANCEMENTS IN IDENTIFYING IN UTERO DEVELOPMENTAL ORIGINS OF CHRONIC ADULT-ONSET DISEASES AFFECTING CARDIOVASCULAR, ENDOCRINE, MUSCULOSKELETAL, AND PSYCHOBEHAVIORAL SYSTEMS. TERATOGEN EXPOSURE IS AN ESTABLISHED PROGRAMMING AGENT FOR ADULT DISEASES, AND RECENT STUDIES SUGGEST THAT PRENATAL ALCOHOL EXPOSURE CORRELATES WITH ADULT ONSET OF NEUROBEHAVIORAL DEFICITS, CARDIOVASCULAR DISEASE, ENDOCRINE DYSFUNCTION, AND NUTRIENT HOMEOSTASIS INSTABILITY, WARRANTING ADDITIONAL INVESTIGATION OF ALCOHOL-INDUCED DOHAD, AS WELL AS PATIENT FOLLOW-UP WELL INTO ADULTHOOD FOR AFFECTED INDIVIDUALS. IN UTERO EPIGENETIC ALTERATIONS DURING CRITICAL PERIODS OF METHYLATION ARE A KEY POTENTIAL MECHANISM FOR PROGRAMMING AND SUSCEPTIBILITY OF ADULT-ONSET CHRONIC DISEASES, WITH IMPRINTED GENES AFFECTING METABOLISM BEING CRITICAL TARGETS. ADDITIONAL STUDIES IN EPIDEMIOLOGY, PHENOTYPIC CHARACTERIZATION IN RESPONSE TO TIMING, DOSE, AND DURATION OF EXPOSURE, AS WELL AS ELUCIDATION OF MECHANISMS UNDERLYING FASD-DOHAD INTER RELATION, ARE THUS NEEDED TO CLINICALLY DEFINE CHRONIC DISEASE ASSOCIATED WITH PRENATAL ALCOHOL EXPOSURE. THESE STUDIES ARE CRITICAL TO ESTABLISH INTERVENTIONAL STRATEGIES THAT DECREASE INCIDENCE OF THESE ADULT-ONSET DISEASES AND PROMOTE HEALTHIER AGING AMONG INDIVIDUALS AFFECTED WITH FASD. 2016 19 4280 26 MICRONUTRIENTS IN EARLY LIFE AND OFFSPRING METABOLIC HEALTH PROGRAMMING: A PROMISING TARGET FOR PREVENTING NON-COMMUNICABLE DISEASES. CHRONIC NON-COMMUNICABLE DISEASES ARE THE LEADING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. DEVELOPING AND IMPLEMENTING EFFECTIVE PREVENTIVE STRATEGIES IS THE BEST WAY TO ENSURE THE OVERALL METABOLIC HEALTH STATUS OF THE POPULATION AND TO COUNTER THE GLOBAL BURDEN OF NON-COMMUNICABLE DISEASES. PREDISPOSITION TO OBESITY AND OTHER NON-COMMUNICABLE DISEASES IS DUE TO A COMBINATION OF GENETIC AND ENVIRONMENTAL FACTORS THROUGHOUT LIFE, BUT THE EARLY ENVIRONMENT, PARTICULARLY THE ENVIRONMENT DURING THE FETAL PERIOD AND THE EARLY YEARS OF LIFE, IS CRUCIAL IN DETERMINING METABOLIC HEALTH, HENCE THE CONCEPT OF 'FETAL PROGRAMMING'. THE ORIGINS OF THIS CAUSAL LINK BETWEEN ENVIRONMENTAL FACTORS AND DISEASE LIE IN EPIGENETIC MECHANISMS. AMONG THE ENVIRONMENTAL FACTORS, DIET PLAYS A CRUCIAL ROLE IN THIS PROCESS. SUBSTANTIAL EVIDENCE DOCUMENTED THE KEY ROLE OF MACRONUTRIENTS IN THE PROGRAMMING OF METABOLIC DISEASES EARLY IN LIFE. RECENTLY, THE EFFECT OF MATERNAL MICRONUTRIENT INTAKE ON OFFSPRING METABOLIC HEALTH IN LATER LIFE EMERGED. THE PURPOSE OF THIS NARRATIVE REVIEW IS TO BRING TO LIGHT AVAILABLE EVIDENCE IN THE LITERATURE ON THE EFFECT OF MATERNAL MICRONUTRIENT STATUS ON OFFSPRING METABOLIC HEALTH AND UNDERLYING EPIGENETIC MECHANISMS THAT DRIVE THIS LINK TO HIGHLIGHT ITS POTENTIAL ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES. 2023 20 6818 29 [FETAL PROGRAMMING AS A CAUSE OF CHRONIC DISEASES IN ADULT LIFE]. LONG-TERM ADAPTIVE CHANGES OCCURRING IN A DEVELOPING FETUS IN RESPONSE TO UNSTABLE IN UTERO ENVIRONMENTAL CONDITIONS, WHICH APPEAR AT A PARTICULAR TIME (CRITICAL WINDOW), ARE CALLED INTRAUTERINE OR FETAL PROGRAMMING. THESE ADAPTIVE CHANGES ARE BENEFICIAL DURING THE INTRAUTERINE PERIOD BECAUSE THEY ADAPT THE FETUS TO CURRENT NEEDS, BUT MAY TURN OUT TO BE HARMFUL IN THE END AND LEAD TO DEVELOPMENT OF CHRONIC DISEASES IN ADULT LIFE. FETAL PROGRAMMING MEANS THE STRUCTURAL AND FUNCTIONAL CHANGING OF AN ORGANISM, METABOLISM AND FUNCTION OF SOME CELLS, TISSUES AND SYSTEMS, THAT OCCUR EVEN DESPITE INTRAUTERINE LIMITATIONS. EVENTS OF FETAL LIFE INFLUENCE THE DETERMINATION OF PHYSIOLOGICAL PATTERNS WHICH MAY MANIFEST AS DISEASE PROCESSES IN THE ADULTHOOD (BARKER'S HYPOTHESIS). GENETIC AND ENVIRONMENTAL FACTORS (POOR DIET IN PREGNANCY CHRONIC INTRAUTERINE FETAL HYPOXIA, THE EFFECTS OF XENOBIOTICS AND DRUGS, AS WELL AS HORMONAL DISORDERS) INFLUENCE THE PHENOTYPE OF A NEWBORN AND ARE INVOLVED IN THE INTRAUTERINE PROGRAMMING PROCESS. THE EFFECTS OF FETAL PROGRAMMING MAY BE PASSED ALONG TO THE NEXT GENERATIONS VIA NOT FULLY UNDERSTOOD PATHWAYS, WHICH PROBABLY INCLUDE EPIGENETIC MECHANISMS. MOST OF THE MECHANISMS UNDERLYING THIS PROCESS REMAIN UNCLEAR AND NEED TO BE ELUCIDATED. 2014