1 6406 167 THE SEARCH FOR RELIABLE BIOMARKERS OF DISEASE IN MULTIPLE CHEMICAL SENSITIVITY AND OTHER ENVIRONMENTAL INTOLERANCES. WHILST FACING A WORLDWIDE FAST INCREASE OF FOOD AND ENVIRONMENTAL ALLERGIES, THE MEDICAL COMMUNITY IS ALSO CONFRONTED WITH ANOTHER INHOMOGENEOUS GROUP OF ENVIRONMENT-ASSOCIATED DISABLING CONDITIONS, INCLUDING MULTIPLE CHEMICAL SENSITIVITY (MCS), FIBROMYALGIA, CHRONIC FATIGUE SYNDROME, ELECTRIC HYPERSENSITIVITY, AMALGAM DISEASE AND OTHERS. THESE SHARE THE FEATURES OF POLY-SYMPTOMATIC MULTI-ORGAN CUTANEOUS AND SYSTEMIC MANIFESTATIONS, WITH POSTULATED INHERITED/ACQUIRED IMPAIRED METABOLISM OF CHEMICAL/PHYSICAL/NUTRITIONAL XENOBIOTICS, TRIGGERING ADVERSE REACTIONS AT EXPOSURE LEVELS FAR BELOW TOXICOLOGICALLY-RELEVANT VALUES, OFTEN IN THE ABSENCE OF CLEAR-CUT ALLERGOLOGIC AND/OR IMMUNOLOGIC INVOLVEMENT. DUE TO THE LACK OF PROVEN PATHOGENIC MECHANISMS GENERATING MEASURABLE DISEASE BIOMARKERS, THESE ENVIRONMENTAL HYPERSENSITIVITIES ARE GENERALLY IGNORED BY SANITARY AND SOCIAL SYSTEMS, AS PSYCHOGENIC OR "MEDICALLY UNEXPLAINED SYMPTOMS". THE UNCONTROLLED APPLICATION OF DIAGNOSTIC AND TREATMENT PROTOCOLS NOT CORRESPONDING TO ACCEPTABLE LEVELS OF VALIDATION, SAFETY, AND CLINICAL EFFICACY, TO A STEADILY INCREASING NUMBER OF PATIENTS DEMANDING ASSISTANCE, OCCURS IN MANY COUNTRIES IN THE ABSENCE OF EVIDENCE-BASED GUIDELINES. HERE WE REVISE AVAILABLE INFORMATION SUPPORTING THE ORGANIC NATURE OF THESE CLINICAL CONDITIONS. FOLLOWING INTENSE RESEARCH ON GENE POLYMORPHISMS OF PHASE I/II DETOXIFICATION ENZYME GENES, SO FAR STATISTICALLY INCONCLUSIVE, EPIGENETIC AND METABOLIC FACTORS ARE UNDER INVESTIGATION, IN PARTICULAR FREE RADICAL/ANTIOXIDANT HOMEOSTASIS DISTURBANCES. THE FINDING OF RELEVANT ALTERATIONS OF CATALASE, GLUTATHIONE-TRANSFERASE AND PEROXIDASE DETOXIFYING ACTIVITIES SIGNIFICANTLY CORRELATING WITH CLINICAL MANIFESTATIONS OF MCS, HAS RECENTLY REGISTERED SOME PROGRESS TOWARDS THE IDENTIFICATION OF RELIABLE BIOMARKERS OF DISEASE ONSET, PROGRESSION, AND TREATMENT OUTCOMES. 2011 2 6867 30 [PARENTAL AGEING AND ASSISTED REPRODUCTION TECHNOLOGIES: ANALYSIS OF RISK OF CHRONIC DISEASES IN THE PROGENY]. CONCEPTION OF A CHILD AT ADVANCED PARENTAL AGE (> 35 YEARS) HAS BEEN STEADILY INCREASING IN RECENT DECADES, ESPECIALLY IN DEVELOPED COUNTRIES. SOCIO-ECONOMIC FACTORS, EFFECTIVE CONTRACEPTIVES, AND THE AVAILABILITY OF ASSISTED REPRODUCTION TECHNOLOGIES (ART) HAVE A DIRECT IMPACT ON POSTPONING THE DECISION TO HAVE A BABY. ART ENABLES REPRODUCTIVE SUCCESS FOR PEOPLE DIAGNOSED AS INFERTILE OR WITH REDUCED POSSIBILITIES OF BECOMING PREGNANT DUE TO CONCOMITANT PATHOLOGIES. EPIDEMIOLOGICAL STUDIES INDICATE THAT BOTH ADVANCED PARENTAL AGE AND ART ARE ASSOCIATED WITH PATHOLOGIES OF PREGNANCY, SUCH AS GESTATIONAL DIABETES, RISK OF PRE-ECLAMPSIA, MISCARRIAGE, PLACENTAL ABRUPTION, PRETERM LABOR, STILLBIRTH, NEURODEVELOPMENTAL DISORDERS AND CHRONIC DISEASE OF THE OFFSPRING. IN OUR WORK, WE WILL FOCUS ON THE AVAILABLE INFORMATION ON METABOLIC CHANGES THAT INCREASE THE RISK OF DEVELOPING CARDIOVASCULAR DISEASES IN THE OFFSPRING OF PARENTS AT AN ADVANCED AGE AND CONCEIVED THROUGH ART. FINALLY, WE WILL ADDRESS THE SOURCES OF THE OBSERVED DISTURBANCES AT THE GAMETE AND EMBRYO LEVEL, RELATED TO OXYGEN STRESS, EPIGENETIC MODIFICATIONS AND DNA DAMAGE, CONSIDERING POSSIBLE RESCUE ACTIONS. 2022 3 3901 30 LEAD (PB) AND NEURODEVELOPMENT: A REVIEW ON EXPOSURE AND BIOMARKERS OF EFFECT (BDNF, HDL) AND SUSCEPTIBILITY. LEAD (PB) IS A UBIQUITOUS ENVIRONMENTAL POLLUTANT AND A POTENT TOXIC COMPOUND. HUMANS ARE EXPOSED TO PB THROUGH INHALATION, INGESTION, AND SKIN CONTACT VIA FOOD, WATER, TOBACCO SMOKE, AIR, DUST, AND SOIL. PB ACCUMULATES IN BONES, BRAIN, LIVER AND KIDNEY. FETAL EXPOSURE OCCURS VIA TRANSPLACENTAL TRANSMISSION. THE MOST CRITICAL HEALTH EFFECTS ARE DEVELOPMENTAL NEUROTOXICITY IN INFANTS AND CARDIOVASCULAR EFFECTS AND NEPHROTOXICITY IN ADULTS. PB EXPOSURE HAS BEEN STEADILY DECREASING OVER THE PAST DECADES, BUT THERE ARE FEW RECENT EXPOSURE DATA FROM THE GENERAL EUROPEAN POPULATION; MOREOVER, NO SAFE PB LIMIT HAS BEEN SET. SENSITIVE BIOMARKERS OF EXPOSURE, EFFECT AND SUSCEPTIBILITY, THAT RELIABLY AND TIMELY INDICATE PB-ASSOCIATED TOXICITY ARE REQUIRED TO ASSESS HUMAN EXPOSURE-HEALTH RELATIONSHIPS IN A SITUATION OF LOW TO MODERATE EXPOSURE. THEREFORE, A SYSTEMATIC LITERATURE REVIEW BASED ON PUBMED ENTRIES PUBLISHED BEFORE JULY 2019 THAT ADDRESSED PB EXPOSURE AND BIOMARKERS OF EFFECT AND SUSCEPTIBILITY, NEURODEVELOPMENTAL TOXICITY, EPIGENETIC MODIFICATIONS, AND TRANSCRIPTOMICS WAS CONDUCTED. FINALLY INCLUDED WERE 58 ORIGINAL PAPERS ON PB EXPOSURE AND 17 STUDIES ON BIOMARKERS. THE BIOMARKERS THAT ARE LINKED TO PB EXPOSURE AND NEURODEVELOPMENT WERE GROUPED INTO EFFECT BIOMARKERS (SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND SERUM/SALIVA CORTISOL), SUSCEPTIBILITY MARKERS (EPIGENETIC MARKERS AND GENE SEQUENCE VARIANTS) AND OTHER BIOMARKERS (SERUM HIGH-DENSITY LIPOPROTEIN (HDL), MATERNAL IRON (FE) AND CALCIUM (CA) STATUS). SERUM BDNF AND PLASMA HDL ARE POTENTIAL CANDIDATES TO BE FURTHER VALIDATED AS EFFECT MARKERS FOR ROUTINE USE IN HBM STUDIES OF PB, COMPLEMENTED BY MARKERS OF FE AND CA STATUS TO ALSO ADDRESS NUTRITIONAL INTERACTIONS RELATED TO NEURODEVELOPMENTAL DISORDERS. FOR SEVERAL MARKERS, A CAUSAL RELATIONSHIP WITH PB-INDUCED NEURODEVELOPMENTAL TOXICITY IS LIKELY. RESULTS ON BDNF ARE DISCUSSED IN RELATION TO ADVERSE OUTCOME PATHWAY (AOP) 13 ("CHRONIC BINDING OF ANTAGONIST TO N-METHYL-D-ASPARTATE RECEPTORS (NMDARS) DURING BRAIN DEVELOPMENT INDUCES IMPAIRMENT OF LEARNING AND MEMORY ABILITIES") OF THE AOP-WIKI. FURTHER STUDIES ARE NEEDED TO VALIDATE SENSITIVE, RELIABLE, AND TIMELY EFFECT BIOMARKERS, ESPECIALLY FOR LOW TO MODERATE PB EXPOSURE SCENARIOS. 2021 4 2708 32 EXERCISE IN NEUROMUSCULAR DISORDERS: A PROMISING INTERVENTION. ALTHOUGH PERFORMING EXERCISE STUDIES IN PATIENTS WITH NEUROMUSCULAR DISORDERS (NMD) IS DIFFICULT, THE NUMBER OF RANDOMIZED CONTROLLED TRIALS IS STEADILY INCREASING. THERE IS GROWING EVIDENCE FOR A POSITIVE EFFECT OF AEROBIC EXERCISE IN SEVERAL NMD, ON THE OTHER HAND, THE EVIDENCE FOR THE EFFECT OF STRENGTH TRAINING IS STILL SCARCE. MANY NMD PATIENTS ARE CAPTURED IN A VICIOUS CIRCLE OF PHYSICAL INACTIVITY, AND IT IS IMPORTANT TO LET PATIENTS ADHERE TO AN ACTIVE LIFESTYLE, IN ORDER TO PREVENT FURTHER CHRONIC CARDIOVASCULAR AND MUSCLE DECONDITIONING AND INCREASED CARDIOVASCULAR HEALTH RISKS. EXERCISE HAS TO BE PRESCRIBED AS IF IT IS MEDICINE, IN ORDER TO INCREASE THE ADHERENCE OF PATIENTS AND TO OPTIMIZE THE EFFICACY OF THE INTERVENTION. EXERCISE IN NMD IS SAFE, ALTHOUGH FOR SOME METABOLIC MYOPATHIES THERE IS A CONTRAINDICATION FOR STRENUOUS EXERCISE. IN NMD KNOWN TO AFFECT CARDIAC MUSCLE, IT IS USUALLY SAFE TO EXERCISE, BUT THE CONSULTATION OF A CARDIOLOGIST IS ADVISED. BASED ON RECENT RESEARCH, AN INCREASE IN PHYSICAL ACTIVITY OF MODERATE INTENSITY AND OF SUFFICIENT DURATION, I.E. A PHYSICALLY ACTIVE LIFESTYLE, COULD BE AT LEAST AS EFFECTIVE AND RELEVANT AS PHYSICAL TRAINING. UNDERLYING MECHANISMS OF EFFECT OF EXERCISE COULD BE THE INFLUENCE OF EPIGENETIC MECHANISMS AND THE ANTI-INFLAMMATORY EFFECT OF EXERCISE, BUT FURTHER STUDIES ARE NEEDED TO CONFIRM THESE HYPOTHESES. 2019 5 2690 34 EVOLUTION OF DOHAD: THE IMPACT OF ENVIRONMENTAL HEALTH SCIENCES. ENVIRONMENTAL EXPOSURES HAVE A SIGNIFICANT INFLUENCE ON THE CHRONIC HEALTH CONDITIONS PLAGUING CHILDREN AND ADULTS. ALTHOUGH THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM HISTORICALLY HAS FOCUSED ON NUTRITION, AN EXPANDING BODY OF RESEARCH SPECIFICALLY COMMUNICATES THE EFFECTS OF CHEMICAL EXPOSURES ON EARLY-LIFE DEVELOPMENT AND THE PROPAGATION OF NON-COMMUNICABLE DISEASE ACROSS THE LIFESPAN. THIS PAPER PROVIDES AN OVERVIEW OF 20 YEARS OF RESEARCH EFFORTS AIMED AT IDENTIFYING CRITICAL WINDOWS OF SUSCEPTIBILITY TO ENVIRONMENTAL EXPOSURES AND THE SIGNALING CHANGES AND EPIGENETIC INFLUENCES ASSOCIATED WITH DISEASE PROGRESSION. DOHAD GRANTS FUNDED BY THE NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES (NIEHS) IN 1991, 2001 AND 2011 ARE IDENTIFIED BY GRANT-ANALYSIS SOFTWARE, AND EACH PORTFOLIO IS ANALYZED FOR EXPOSURES, DISEASE ENDPOINTS, WINDOWS OF EXPOSURE, STUDY DESIGN AND IMPACT ON THE FIELD BASED ON PUBLICATION DATA. RESULTS SHOW THAT THE 1991 AND 2001 PORTFOLIOS COMPRISED METALS, PCBS AND AIR POLLUTANTS; HOWEVER, BY 2011, THE PORTFOLIO HAS EVOLVED TO INCLUDE OR EXPAND THE VARIETY OF ENDOCRINE DISRUPTORS, PESTICIDES/PERSISTENT ORGANIC POLLUTANTS AND METALS. AN ASSORTMENT OF BRAIN-HEALTH ENDPOINTS IS MOST TARGETED ACROSS THE PORTFOLIOS, WHEREAS REPRODUCTION AND CANCER INCREASE STEADILY OVER THE SAME TIME PERIOD, AND NEW ENDPOINTS LIKE OBESITY ARE INTRODUCED BY 2011. WITH MOUNTING EVIDENCE CONNECTING EARLY-LIFE EXPOSURES TO LATER-LIFE DISEASE, WE CONCLUDE THAT IT IS CRITICAL TO EXPAND THE ORIGINAL DOHAD CONCEPT TO INCLUDE ENVIRONMENTAL CHEMICAL EXPOSURES, AND TO CONTINUE A RESEARCH AGENDA THAT EMPHASIZES DEFINING SENSITIVE WINDOWS OF EXPOSURE AND THE MECHANISMS THAT CAUSE DISEASE. 2015 6 4080 20 MATERNAL LIFESTYLE INTERVENTIONS: TARGETING PRECONCEPTION HEALTH. ABOUT ONE-THIRD OF WOMEN OF REPRODUCTIVE AGE ARE OBESE, PREDISPOSING BOTH MOTHER AND BABY TO UNFAVOURABLE PREGNANCY OUTCOMES AND INITIATING AN INTERGENERATIONAL CYCLE OF CHRONIC METABOLIC DISORDERS. HERE WE SUMMARISE RECENT RESEARCH ON THE INFLUENCE OF MATERNAL METABOLIC HEALTH ON OFFSPRING SUSCEPTIBILITY TO FUTURE CARDIOMETABOLIC DISEASES. CURRENT PRIMARY LIFESTYLE APPROACHES (I.E., DIET AND EXERCISE INTERVENTIONS) TO HALT THE SUCCESSION OF INHERITED AND EPIGENETIC METABOLIC ABNORMALITIES HAVE MET WITH LIMITED SUCCESS DUE TO LATE IMPLEMENTATION, POOR ADHERENCE, AND/OR GENERIC GUIDELINES. IN OUR OPINION, SUCH INTERVENTIONS MUST COMMENCE PRIOR TO CONCEPTION TO IMPROVE BOTH MATERNAL AND CHILD HEALTH OUTCOMES, WITH NEW APPROACHES URGENTLY NEEDED TO INCREASE ADHERENCE TO PRIMARY LIFESTYLE CHANGES AMONG REPRODUCTIVE-AGE WOMEN. 2020 7 4051 29 MALE OBESITY: EPIGENETIC ORIGIN AND EFFECTS IN SPERM AND OFFSPRING. PURPOSE OF REVIEW: THE PREVALENCE OF OBESITY HAS INCREASED SUBSTANTIALLY IN THE CURRENT GENERATIONS OF WESTERN COUNTRIES, AND THE BURDEN OF OBESITY-RELATED COMPLICATIONS HAS BEEN GROWING STEADILY. IN MEN, OBESITY IS NOT ONLY A MAJOR RISK FACTOR FOR SERIOUS CHRONIC DISEASES, CONCERN IS GROWING THAT THE REPRODUCTIVE CAPACITY, AND MORE PARTICULARLY, THEIR OFFSPRING'S HEALTH MAY BE AFFECTED. OBESITY-RELATED IMPAIRED SPERMATOGENESIS IS ASSOCIATED WITH A DECREASE IN MICROSCOPIC AND MOLECULAR SPERM CHARACTERISTICS AND PREGNANCY SUCCESS. WE HYPOTHESIZE THAT EPIGENETICS IS AN IMPORTANT MEDIATOR EXPLAINING INTERACTIONS BETWEEN AN OBESOGENIC ENVIRONMENT AND SPERM/OFFSPRING OUTCOMES. RECENT FINDINGS: RECENT STUDIES HAVE EXPLORED INTER- AND TRANSGENERATIONAL EPIGENETIC EFFECTS IN SPERM CELLS AND IN OFFSPRING. FATHER-TO-CHILD EFFECTS HAVE BEEN REPORTED IN RELATION TO PRECONCEPTIONAL NUTRITIONAL AND LIFE-STYLE RELATED FACTORS. SUMMARY: HERE, WE SUMMARIZE THE CURRENT UNDERSTANDING ABOUT OBESITY AND MOLECULAR OR EPIGENETIC UNDERLYING MECHANISMS IN SPERM. WE IDENTIFY THE OBESOGENIC ENVIRONMENT OF THE FATHER BEFORE CONCEPTION AS A POTENTIAL ORIGIN OF HEALTH OR DISEASE IN THE OFFSPRING AND INCLUDE IT AS PART OF A NEW CONCEPT, THE PATERNAL ORIGINS OF HEALTH AND DISEASE (POHAD). 2017 8 363 28 AMBIENT AIR POLLUTION: HEALTH HAZARDS TO CHILDREN. AMBIENT AIR POLLUTION IS PRODUCED BY SOURCES INCLUDING VEHICULAR TRAFFIC, COAL-FIRED POWER PLANTS, HYDRAULIC FRACTURING, AGRICULTURAL PRODUCTION, AND FOREST FIRES. IT CONSISTS OF PRIMARY POLLUTANTS GENERATED BY COMBUSTION AND SECONDARY POLLUTANTS FORMED IN THE ATMOSPHERE FROM PRECURSOR GASES. AIR POLLUTION CAUSES AND EXACERBATES CLIMATE CHANGE, AND CLIMATE CHANGE WORSENS HEALTH EFFECTS OF AIR POLLUTION. INFANTS AND CHILDREN ARE UNIQUELY SENSITIVE TO AIR POLLUTION, BECAUSE THEIR ORGANS ARE DEVELOPING AND THEY HAVE HIGHER AIR PER BODY WEIGHT INTAKE. HEALTH EFFECTS LINKED TO AIR POLLUTION INCLUDE NOT ONLY EXACERBATIONS OF RESPIRATORY DISEASES BUT ALSO REDUCED LUNG FUNCTION DEVELOPMENT AND INCREASED ASTHMA INCIDENCE. ADDITIONAL OUTCOMES OF CONCERN INCLUDE PRETERM BIRTH, LOW BIRTH WEIGHT, NEURODEVELOPMENTAL DISORDERS, IQ LOSS, PEDIATRIC CANCERS, AND INCREASED RISKS FOR ADULT CHRONIC DISEASES. THESE EFFECTS ARE MEDIATED BY OXIDATIVE STRESS, CHRONIC INFLAMMATION, ENDOCRINE DISRUPTION, AND GENETIC AND EPIGENETIC MECHANISMS ACROSS THE LIFE SPAN. NATURAL EXPERIMENTS DEMONSTRATE THAT WITH INITIATIVES SUCH AS INCREASED USE OF PUBLIC TRANSPORTATION, BOTH AIR QUALITY AND COMMUNITY HEALTH IMPROVE. SIMILARLY, THE CLEAN AIR ACT HAS IMPROVED AIR QUALITY, ALTHOUGH EXPOSURE INEQUITIES PERSIST. OTHER EFFECTIVE STRATEGIES FOR REDUCING AIR POLLUTION INCLUDE ENDING RELIANCE ON COAL, OIL, AND GAS; REGULATING INDUSTRIAL EMISSIONS; REDUCING EXPOSURE WITH ATTENTION TO PROXIMITY OF RESIDENCES, SCHOOLS, AND CHILD CARE FACILITIES TO TRAFFIC; AND A GREATER AWARENESS OF THE AIR QUALITY INDEX. THIS POLICY REVIEWS BOTH SHORT- AND LONG-TERM HEALTH CONSEQUENCES OF AMBIENT AIR POLLUTION, ESPECIALLY IN RELATION TO DEVELOPMENTAL EXPOSURES. IT EXAMINES INDIVIDUAL, COMMUNITY, AND LEGISLATIVE STRATEGIES TO MITIGATE AIR POLLUTION. 2021 9 3566 27 IMPACT OF HEAVY METALS ON THE FEMALE REPRODUCTIVE SYSTEM. INTRODUCTION: IT HAS BEEN RECOGNIZED THAT ENVIRONMENTAL POLLUTION CAN AFFECT THE QUALITY OF HEALTH OF THE HUMAN POPULATION. HEAVY METALS ARE AMONG THE GROUP OF HIGHLY EMITTED CONTAMINANTS AND THEIR ADVERSE EFFECT OF LIVING ORGANISMS HAS BEEN WIDELY STUDIED IN RECENT DECADES. LIFESTYLE AND QUALITY OF THE AMBIENT ENVIRONMENT ARE AMONG THESE FACTORS WHICH CAN MAINLY CONTRIBUTE TO THE HEAVY METALS EXPOSURE IN HUMANS. OBJECTIVE: A REVIEW OF LITERATURE LINKING HEAVY METALS AND THE FEMALE REPRODUCTIVE SYSTEM AND DESCRIPTION OF THE POSSIBLE ASSOCIATIONS WITH EMISSION AND EXPOSURE OF HEAVY METALS AND IMPAIRMENTS OF FEMALE REPRODUCTIVE SYSTEM ACCORDING TO CURRENT KNOWLEDGE. RESULTS: THE POTENTIAL HEALTH DISORDERS CAUSED BY CHRONIC OR ACUTE HEAVY METALS TOXICITY INCLUDE IMMUNODEFICIENCY, OSTEOPOROSIS, NEURODEGENERATION AND ORGAN FAILURES. POTENTIAL LINKAGES OF HEAVY METALS CONCENTRATION FOUND IN DIFFERENT HUMAN ORGANS AND BLOOD WITH OESTROGEN-DEPENDENT DISEASES SUCH AS BREAST CANCER, ENDOMETRIAL CANCER, ENDOMETRIOSIS AND SPONTANEOUS ABORTIONS, AS WELL AS PRE-TERM DELIVERIES, STILLBIRTHS AND HYPOTROPHY, HAVE ALSO BEEN REPORTED. CONCLUSIONS: ENVIRONMENTAL DETERIORATION CAN LEAD TO THE ELEVATED RISK OF HUMAN EXPOSURE TO HEAVY METALS, AND CONSEQUENTLY, HEALTH IMPLICATIONS INCLUDING DISTURBANCES IN REPRODUCTION. IT IS THEREFORE IMPORTANT TO CONTINUE THE INVESTIGATIONS ON METAL-INDUCED MECHANISMS OF FERTILITY IMPAIRMENT ON THE GENETIC, EPIGENETIC AND BIOCHEMICAL LEVEL. 2015 10 4803 27 OBESITY AND MALE INFERTILITY. THE WORLDWIDE PREVALENCE OF OBESITY IS INCREASING AMONG BOTH SEXES, WITH ASSOCIATED IMPACTS ON CHRONIC HEALTH AND MEDICAL COMORBIDITIES. SIMILARLY, THE EFFECTS OF OBESITY ON REPRODUCTIVE HEALTH ARE INCREASINGLY BEING RECOGNIZED. ADIPOSITY IS ASSOCIATED WITH REDUCED FERTILITY IN MEN, WITH A COMPLEX AND MULTIFACTORIAL ETIOLOGY. THE REPORTED EFFECTS OF OBESITY ON SEMEN PARAMETERS AND IMPAIRED FERTILITY ARE CONTRASTING, WITH SOME STUDIES SHOWING A CLEAR REDUCTION IN REPRODUCTIVE OUTCOMES ASSOCIATED WITH INCREASED BODY MASS INDEX, WHILE OTHERS DO NOT SHOW SUCH IMPACTS. THESE CONTROVERSIES MAY BE DUE TO THE COMPLEX PATHOPHYSIOLOGY AND INTERPLAY BETWEEN GONADOTROPINS AND END ORGANS, AS WELL AS GENETIC AND EPIGENETIC CHANGES AND OXIDATIVE STRESS ON MALE FERTILITY AND FUNCTION. THESE DIFFERENT ASPECTS HAVE LED TO HETEROGENEOUS PARTICIPANTS IN STUDIES AND VARYING IMPLICATIONS FOR ASSISTED REPRODUCTIVE OUTCOMES AS WELL AS OFFSPRING HEALTH. TREATMENT MODALITIES TO MANAGE OBESITY INCLUDE LIFESTYLE, MEDICAL, AND SURGICAL OPTIONS, WITH EMERGING AND EFFECTIVE MEDICAL TREATMENTS SHOWING PROMISE IN REPRODUCTIVE OUTCOMES. 2023 11 3595 22 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 12 4863 32 ORIGINS OF LIFETIME HEALTH AROUND THE TIME OF CONCEPTION: CAUSES AND CONSEQUENCES. PARENTAL ENVIRONMENTAL FACTORS, INCLUDING DIET, BODY COMPOSITION, METABOLISM, AND STRESS, AFFECT THE HEALTH AND CHRONIC DISEASE RISK OF PEOPLE THROUGHOUT THEIR LIVES, AS CAPTURED IN THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE CONCEPT. RESEARCH ACROSS THE EPIDEMIOLOGICAL, CLINICAL, AND BASIC SCIENCE FIELDS HAS IDENTIFIED THE PERIOD AROUND CONCEPTION AS BEING CRUCIAL FOR THE PROCESSES MEDIATING PARENTAL INFLUENCES ON THE HEALTH OF THE NEXT GENERATION. DURING THIS TIME, FROM THE MATURATION OF GAMETES THROUGH TO EARLY EMBRYONIC DEVELOPMENT, PARENTAL LIFESTYLE CAN ADVERSELY INFLUENCE LONG-TERM RISKS OF OFFSPRING CARDIOVASCULAR, METABOLIC, IMMUNE, AND NEUROLOGICAL MORBIDITIES, OFTEN TERMED DEVELOPMENTAL PROGRAMMING. WE REVIEW PERICONCEPTIONAL INDUCTION OF DISEASE RISK FROM FOUR BROAD EXPOSURES: MATERNAL OVERNUTRITION AND OBESITY; MATERNAL UNDERNUTRITION; RELATED PATERNAL FACTORS; AND THE USE OF ASSISTED REPRODUCTIVE TREATMENT. STUDIES IN BOTH HUMANS AND ANIMAL MODELS HAVE DEMONSTRATED THE UNDERLYING BIOLOGICAL MECHANISMS, INCLUDING EPIGENETIC, CELLULAR, PHYSIOLOGICAL, AND METABOLIC PROCESSES. WE ALSO PRESENT A META-ANALYSIS OF MOUSE PATERNAL AND MATERNAL PROTEIN UNDERNUTRITION THAT SUGGESTS DISTINCT PARENTAL PERICONCEPTIONAL CONTRIBUTIONS TO POSTNATAL OUTCOMES. WE PROPOSE THAT THE EVIDENCE FOR PERICONCEPTIONAL EFFECTS ON LIFETIME HEALTH IS NOW SO COMPELLING THAT IT CALLS FOR NEW GUIDANCE ON PARENTAL PREPARATION FOR PREGNANCY, BEGINNING BEFORE CONCEPTION, TO PROTECT THE HEALTH OF OFFSPRING. 2018 13 6173 29 THE HEALTH OUTCOMES OF HUMAN OFFSPRING CONCEIVED BY ASSISTED REPRODUCTIVE TECHNOLOGIES (ART). CONCERNS HAVE BEEN RAISED ABOUT THE HEALTH AND DEVELOPMENT OF CHILDREN CONCEIVED BY ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) SINCE 1978. CONTROVERSIALLY, ART HAS BEEN LINKED WITH ADVERSE OBSTETRIC AND PERINATAL OUTCOMES, AN INCREASED RISK OF BIRTH DEFECTS, CANCERS, AND GROWTH AND DEVELOPMENT DISORDERS. EMERGING EVIDENCE SUGGESTS THAT ART TREATMENT MAY ALSO PREDISPOSE INDIVIDUALS TO AN INCREASED RISK OF CHRONIC AGEING RELATED DISEASES SUCH AS OBESITY, TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE. THIS REVIEW WILL SUMMARIZE THE AVAILABLE EVIDENCE ON THE SHORT-TERM AND LONG-TERM HEALTH OUTCOMES OF ART SINGLETONS, AS MULTIPLE PREGNANCIES AFTER MULTIPLE EMBRYOS TRANSFER, ARE ASSOCIATED WITH LOW BIRTH WEIGHT AND PRETERM DELIVERY, WHICH CAN SEPARATELY INCREASE RISK OF ADVERSE POSTNATAL OUTCOMES, AND IMPACT LONG-TERM HEALTH. WE WILL ALSO EXAMINE THE POTENTIAL FACTORS THAT MAY CONTRIBUTE TO THESE HEALTH RISKS, AND DISCUSS UNDERLYING MECHANISMS, INCLUDING EPIGENETIC CHANGES THAT MAY OCCUR DURING THE PREIMPLANTATION PERIOD AND REPROGRAM DEVELOPMENT IN UTERO, AND ADULT HEALTH, LATER IN LIFE. LASTLY, THIS REVIEW WILL CONSIDER THE FUTURE DIRECTIONS WITH THE VIEW TO OPTIMIZE THE LONG-TERM HEALTH OF ART CHILDREN. 2017 14 2801 23 FEMALE OBESITY: SHORT- AND LONG-TERM CONSEQUENCES ON THE OFFSPRING. THE WORLDWIDE PREVALENCE OF OBESITY HAS RISEN OVER THE PAST FEW DECADES AND WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. PRE-PREGNANCY OBESITY AND EXCESSIVE GESTATIONAL WEIGHT GAIN INCREASE MISCARRIAGE RATES AND OBSTETRIC AND NEONATAL COMPLICATIONS, WHICH RESULT IN A LOWER HEALTHY LIVE BIRTH RATE. IN ADDITION TO ITS NEGATIVE CONSEQUENCES FOR THE MOTHER, OBESITY HAS BEEN SHOWN TO BE AN IMPORTANT RISK FACTOR FOR CHRONIC ILLNESSES, SUCH AS CARDIOVASCULAR DISEASE, METABOLIC SYNDROME AND TYPE 2 DIABETES IN THE ADOLESCENCE AND ADULTHOOD OF THE OFFSPRING. MOREOVER, MATERNAL OBESITY CAUSES PSYCHOLOGICAL PROBLEMS, PHYSICAL DISABILITIES AND HIGHER HEALTHCARE COSTS. FETAL PROGRAMMING OF METABOLIC FUNCTION INDUCED BY OBESITY, THROUGH PHYSIOLOGICAL AND/OR EPIGENETIC MECHANISMS, MAY HAVE AN INTERGENERATIONAL EFFECT AND COULD, THUS, PERPETUATE OBESITY IN THE NEXT GENERATION. IN ORDER TO BREAK THIS VICIOUS CIRCLE AND AVOID SERIOUS SHORT- AND LONG-TERM NEGATIVE OUTCOMES FOR BOTH MOTHERS AND FETUSES, THE PREVENTION AND ADEQUATE MANAGEMENT OF OBESITY AND GESTATIONAL WEIGHT GAIN ARE ESSENTIAL. 2013 15 3578 26 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 16 6873 28 [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 17 1915 26 ENVIRONMENTAL AND OCCUPATIONAL EXPOSURE OF METALS AND FEMALE REPRODUCTIVE HEALTH. UNTAINTED ENVIRONMENT PROMOTES HEALTH, BUT THE LAST FEW DECADES EXPERIENCED STEEP UPSURGE IN ENVIRONMENTAL CONTAMINANTS POSING DETRIMENTAL PHYSIOLOGICAL IMPACT. THE RESPONSIBLE FACTORS MAINLY INCLUDE THE EXPONENTIAL GROWTH OF HUMAN POPULATION, HAVOC RISE IN INDUSTRIALIZATION, POORLY PLANNED URBANIZATION, AND SLAPDASH ENVIRONMENT MANAGEMENT. ENVIRONMENTAL DEGRADATION CAN INCREASE THE LIKELIHOOD OF HUMAN EXPOSURE TO HEAVY METALS, RESULTING IN HEALTH CONSEQUENCES SUCH AS REPRODUCTIVE PROBLEMS. AS A RESULT, RESEARCH INTO METAL-INDUCED CAUSES OF REPRODUCTIVE IMPAIRMENT AT THE GENETIC, EPIGENETIC, AND BIOCHEMICAL LEVELS MUST BE STRENGTHENED FURTHER. THESE METALS IMPACT UPON THE FEMALE REPRODUCTION AT ALL STRATA OF ITS REGULATION AND FUNCTIONS, BE IT DEVELOPMENT, MATURATION, OR ENDOCRINE FUNCTIONS, AND ARE LINKED TO AN INCREASE IN THE CAUSES OF INFERTILITY IN WOMEN. CHRONIC EXPOSURES TO THE HEAVY METALS MAY LEAD TO BREAST CANCER, ENDOMETRIOSIS, ENDOMETRIAL CANCER, MENSTRUAL DISORDERS, AND SPONTANEOUS ABORTIONS, AS WELL AS PRE-TERM DELIVERIES, STILLBIRTHS. FOR EXAMPLE, ENDOMETRIOSIS, ENDOMETRIAL CANCER, AND SPONTANEOUS ABORTIONS ARE ALL CAUSED BY THE METALLOESTROGEN CADMIUM (CD); LEAD (PB) LEVELS OVER A CERTAIN THRESHOLD CAN CAUSE SPONTANEOUS ABORTION AND HAVE A TERATOGENIC IMPACT; TOXIC AMOUNTS OF MERCURY (HG) HAVE AN INFLUENCE ON THE MENSTRUAL CYCLE, WHICH CAN LEAD TO INFERTILITY. IMPACT OF ENVIRONMENTAL EXPOSURE TO HEAVY METALS ON FEMALE FERTILITY IS THEREFORE A WELL-KNOWN FACT. THUS, THE UNDERLYING MECHANISMS MUST BE EXPLAINED AND PERIODICALLY UPDATED, GIVEN THE GROWING EVIDENCE ON THE INFLUENCE OF INCREASING ENVIRONMENTAL HEAVY METAL LOAD ON FEMALE FERTILITY. THE PURPOSE OF THIS REVIEW IS TO GIVE A CONCISE OVERVIEW OF HOW HEAVY METAL AFFECTS FEMALE REPRODUCTIVE HEALTH. 2022 18 529 22 ASTHMA IN URBAN CHILDREN: EPIDEMIOLOGY, ENVIRONMENTAL RISK FACTORS, AND THE PUBLIC HEALTH DOMAIN. ASTHMA IS THE MOST COMMONLY REPORTED CHRONIC CONDITION OF CHILDHOOD IN DEVELOPED COUNTRIES, WITH 6.5 MILLION CHILDREN AFFECTED IN THE USA. A DISPARATE BURDEN OF CHILDHOOD ASTHMA IS SEEN AMONG SOCIOECONOMICALLY DISADVANTAGED YOUTH, OFTEN CONCENTRATED IN URBAN AREAS WITH HIGH POVERTY RATES. HOST FACTORS THAT PREDISPOSE A CHILD TO ASTHMA INCLUDE ATOPY, MALE GENDER, PARENTAL HISTORY OF ASTHMA, AND ALSO RACE, ETHNICITY, AND GENETIC AND EPIGENETIC SUSCEPTIBILITIES. ENVIRONMENTAL FACTORS, SUCH AS IMPROVED HYGIENE, AMBIENT AIR POLLUTION, AND EARLY LIFE EXPOSURES TO MICROBES AND AEROALLERGENS, ALSO INFLUENCE THE DEVELOPMENT OF ASTHMA. WITH GREATER THAN 90% OF TIME SPENT INDOORS, HOME EXPOSURES (SUCH AS COCKROACH, RODENT, AND INDOOR AIR POLLUTION) ARE HIGHLY RELEVANT FOR URBAN ASTHMA. MORBIDITY REDUCTION MAY REQUIRE FOCUSED PUBLIC HEALTH INITIATIVES FOR ENVIRONMENTAL INTERVENTION IN HIGH PRIORITY RISK GROUPS AND THE ADDITION OF IMMUNE MODULATORY AGENTS IN CHILDREN WITH POORLY CONTROLLED DISEASE. 2016 19 360 22 AMBIENT AIR POLLUTION AND BIOMARKERS OF HEALTH EFFECT. RECENTLY, THE AIR POLLUTION SITUATION OF OUR COUNTRY IS VERY SERIOUS ALONG WITH THE DEVELOPMENT OF URBANIZATION AND INDUSTRIALIZATION. STUDIES INDICATE THAT THE EXPOSURE OF AIR POLLUTION CAN CAUSE A RISE OF INCIDENCE AND MORTALITY OF MANY DISEASES, SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), ASTHMA, MYOCARDIAL INFARCTION, AND SO ON. HOWEVER, THERE IS NOW GROWING EVIDENCE SHOWING THAT SIGNIFICANT AIR POLLUTION EXPOSURES ARE ASSOCIATED WITH EARLY BIOMARKERS IN VARIOUS SYSTEMS OF THE BODY. IN ORDER TO BETTER PREVENT AND CONTROL THE DAMAGE EFFECT OF AIR POLLUTION, THIS ARTICLE SUMMARIZES COMPREHENSIVELY EPIDEMIOLOGICAL STUDIES ABOUT THE BAD EFFECTS ON THE BIOMARKERS OF RESPIRATORY SYSTEM, CARDIOVASCULAR SYSTEM, AND GENETIC AND EPIGENETIC SYSTEM EXPOSURE TO AMBIENT AIR POLLUTION. 2017 20 4804 17 OBESITY AND MALE INFERTILITY: MECHANISMS AND MANAGEMENT. OBESITY IS CONSIDERED A GLOBAL HEALTH PROBLEM AFFECTING MORE THAN A THIRD OF THE POPULATION. COMPLICATIONS OF OBESITY INCLUDE CARDIOVASCULAR DISEASES, TYPE 2 DIABETES MELLITUS, MALIGNANCY (INCLUDING PROSTATIC CANCER), NEURODEGENERATION AND ACCELERATED AGEING. IN MALES, THESE FURTHER INCLUDE ERECTILE DYSFUNCTION, POOR SEMEN QUALITY AND SUBCLINICAL PROSTATITIS. ALTHOUGH POORLY UNDERSTOOD, IMPORTANT MEDIATORS OF OBESITY THAT MAY INFLUENCE THE MALE REPRODUCTIVE SYSTEM INCLUDE HYPERINSULINEMIA, HYPERLEPTINEMIA, CHRONIC INFLAMMATION AND OXIDATIVE STRESS. OBESITY IS KNOWN TO DISRUPT MALE FERTILITY AND THE REPRODUCTION POTENTIAL, PARTICULARLY THROUGH ALTERATION IN THE HYPOTHALAMIC-PITUITARY-GONADAL AXIS, DISRUPTION OF TESTICULAR STEROIDOGENESIS AND METABOLIC DYSREGULATION, INCLUDING INSULIN, CYTOKINES AND ADIPOKINES. IMPORTANTLY, OBESITY AND ITS UNDERLYING MEDIATORS RESULT IN A NEGATIVE IMPACT ON SEMEN PARAMETERS, INCLUDING SPERM CONCENTRATION, MOTILITY, VIABILITY AND NORMAL MORPHOLOGY. MOREOVER, OBESITY INHIBITS CHROMATIN CONDENSATION, DNA FRAGMENTATION, INCREASES APOPTOSIS AND EPIGENETIC CHANGES THAT CAN BE TRANSFERRED TO THE OFFSPRING. THIS REVIEW DISCUSSES THE IMPACT OF OBESITY ON THE MALE REPRODUCTIVE SYSTEM AND FERTILITY, INCLUDING ASSOCIATED MECHANISMS. FURTHERMORE, WEIGHT MANAGEMENT STRATEGIES, LIFESTYLE CHANGES, PRESCRIPTION MEDICATION, AND COMPLEMENTARY AND ALTERNATIVE MEDICINE IN THE MANAGEMENT OF OBESITY-INDUCED SUBFERTILITY IS DISCUSSED. 2021