1  3586 278 IMPACT OF THE POLYCARBONATE STRIPPERS USED IN ASSISTED REPRODUCTION TECHNIQUES ON EMBRYONIC DEVELOPMENT. STUDY QUESTION: DO DAILY MANIPULATIONS OF PREIMPLANTATION EMBRYOS WITH POLYCARBONATE (PC)-MADE BISPHENOL A (BPA)-RELEASING STRIPPERS INFLUENCE EMBRYO DEVELOPMENT? SUMMARY ANSWER: COMPARED TO GLASS STRIPPERS, PC STRIPPERS ENHANCE THE BLASTOCYST DEVELOPMENT RATE BUT THIS DOES NOT SEEM TO BE BPA-RELATED. WHAT IS KNOWN ALREADY: PC STRIPPERS HAVE BEEN SHOWN TO RELEASE TINY AMOUNTS (AROUND 0.5 NG/ML BPA) OF BPA IN ROUTINE HUMAN IVF PROCEDURES. A CHRONIC EXPOSURE TO BPA EITHER IN VIVO OR IN VITRO DURING THE PREIMPLANTATION PERIOD CAN IMPACT POST-IMPLANTATION AND POST-NATAL DEVELOPMENT. BPA CAN ACT RAPIDLY BY BINDING TO MEMBRANE RECEPTORS AND INDUCING RAPID NON-GENOMIC EFFECTS. STUDY DESIGN, SIZE, DURATION: THIS EXPERIMENTAL STUDY USING MOUSE EMBRYOS HAD A BALANCED DESIGN AND BLINDED EVALUATIONS OF THE ENDPOINTS. PARTICIPANTS/MATERIALS, SETTING, METHODS: IN VIVO FERTILIZED ZYGOTES WERE OBTAINED FROM OUTBRED SWISS CD1 MICE CROSSINGS AFTER AN OVARIAN STIMULATION. THE ZYGOTES WERE ALLOCATED TO THREE DAILY HANDLING CONDITIONS (HCS) AND CULTURED UNTIL DAY 4 IN A SINGLE HUMAN COMMERCIAL MEDIUM. EACH DAY, THE EMBRYOS WERE HANDLED FOR 20 S EITHER IN A PC STRIPPER (HC1) OR IN A GLASS STRIPPER (HC2). IN HC3, THE EMBRYOS WERE PRE-EXPOSED TO 0.5 NG/ML BPA BEFORE BEING HANDLED FOR 20 S IN A GLASS STRIPPER. HANDLING OPERATIONS WERE REPEATED ON DAYS 1, 2 AND 3. EMBRYO DEVELOPMENT WAS ASSESSED BLINDLY ON DAY 4. EXPANDED BLASTOCYSTS WERE SELECTED FOR A TRANSCRIPTOMIC ANALYSIS USING AGILENT SUREPRINT G3 MOUSE GE V2 MICROARRAYS AND THE RETROTRANSPOSON LINE1-ORF2 EXPRESSION WAS ANALYSED USING QRT-PCR, AS A PROXY FOR A GLOBAL EVALUATION OF THE EPIGENETIC STATUS. MAIN RESULTS AND THE ROLE OF CHANCE: COMPARED TO THE EMBRYOS MANIPULATED IN HC2 (N = 243), THOSE IN HC1 (N = 228) DEVELOPED SIGNIFICANTLY MORE OFTEN TO THE BLASTOCYST STAGE (55 VS 46%; P < 0.05). IT APPEARS THE EFFECT OF THESE PC STRIPPERS WAS NOT BPA-RELATED BECAUSE EMBRYOS PRE-EXPOSED TO BPA (HC3, N = 230) SHOWED NO DIFFERENCE IN THE BLASTOCYST RATE WHEN COMPARED TO HC2 (43 VS 46%). WHEN ANALYSING SAME-STAGE BLASTOCYSTS, WE NOTICED NO DIFFERENCE IN THE EMBRYO GENE EXPRESSION BETWEEN THE THREE HC GROUPS. LARGE SCALE DATA: HTTPS://WWW.NCBI.NLM.NIH.GOV/GEO/QUERY/ACC.CGI?ACC=GSE148868. LIMITATIONS, REASONS FOR CAUTION: OUR RESULTS USING A MOUSE MODEL DESIGNED TO MIMIC HUMAN CONDITIONS (OUTBRED STRAIN, HUMAN COMMERCIAL IVF DISHES AND A UNIQUE COMMERCIAL HUMAN EMBRYONIC CULTURE MEDIA) ARE REASSURING SINCE NO GENE WAS FOUND TO BE DIFFERENTIALLY EXPRESSED, INCLUDING LINE-1 GENES, AS A PROXY FOR A GLOBAL EVALUATION OF THE EPIGENETIC STATUS. HOWEVER, NO GLOBAL EPIGENETIC ANALYSIS OF THE GENOME HAS BEEN PERFORMED. FURTHERMORE, WE DID NOT EVALUATE POST-IMPLANTATION EVENTS, ALTHOUGH BPA EXPOSURE DURING PERI-CONCEPTION COULD AFFECT FOETO-PLACENTAL AND POST-NATAL DEVELOPMENT. WIDER IMPLICATIONS OF THE FINDINGS: BASED ON THE PRECAUTIONARY PRINCIPLE, SEVERAL EUROPEAN COUNTRIES BANNED THE USE OF BPA IN BABY BOTTLES AND FOOD PACKAGING SEVERAL YEARS BEFORE EUROPEAN AGENCIES TOOK AN OFFICIAL POSITION. THE QUESTION OF APPLYING THIS PRINCIPLE TO PLASTICS IN CLOSED CONTACT WITH HUMAN EMBRYOS IS RAISED. FURTHER STUDIES ARE NEEDED FOR A DECISION TO BE MADE. STUDY FUNDING/COMPETING INTEREST(S): THIS STUDY WAS SUPPORTED BY A GRANT FROM THE AGENCE DE BIOMEDECINE (AOR 2016). THE AUTHORS DECLARE NO COMPETING INTEREST.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
2  6384  46 THE ROLE OF POLYCARBONATE MONOMER BISPHENOL-A IN INSULIN RESISTANCE. BISPHENOL A (BPA) IS A SYNTHETIC UNIT OF POLYCARBONATE POLYMERS AND EPOXY RESINS, THE TYPES OF PLASTICS THAT COULD BE FOUND IN ESSENTIALLY EVERY HUMAN POPULATION AND INCORPORATED INTO ALMOST EVERY ASPECT OF THE MODERN HUMAN SOCIETY. BPA POLYMERS APPEAR IN A WIDE RANGE OF PRODUCTS, FROM LIQUID STORAGES (PLASTIC BOTTLES, CAN AND GLASS LININGS, WATER PIPES AND TANKS) AND FOOD STORAGES (PLASTICS WRAPS AND CONTAINERS), TO MEDICAL AND DENTAL DEVICES. BPA POLYMERS COULD BE HYDROLYZED SPONTANEOUSLY OR IN A PHOTO- OR TEMPERATURE-CATALYZED PROCESS, PROVIDING WIDESPREAD ENVIRONMENTAL DISTRIBUTION AND CHRONIC EXPOSURE TO THE BPA MONOMER IN CONTEMPORARY HUMAN POPULATIONS. BISPHENOL A IS ALSO A XENOESTROGEN, AN ENDOCRINE-DISRUPTING CHEMICAL (EDC) THAT INTERFERES WITH THE ENDOCRINE SYSTEM MIMICKING THE EFFECTS OF AN ESTROGEN AND COULD POTENTIALLY KEEP OUR ENDOCRINE SYSTEM IN A CONSTANT PERTURBATION THAT PARALLELS ENDOCRINE DISRUPTION ARISING DURING PREGNANCY, SUCH AS INSULIN RESISTANCE (IR). GESTATIONAL INSULIN RESISTANCE REPRESENTS A NATURAL BIOLOGICAL PHENOMENON OF HIGHER INSULIN RESISTANCE IN PERIPHERAL TISSUES OF THE PREGNANT FEMALES, WHEN NUTRIENTS ARE INCREASINGLY BEING DIRECTED TO THE EMBRYO INSTEAD OF BEING STORED IN PERIPHERAL TISSUES. GESTATIONAL DIABETES MELLITUS MAY APPEAR IN HEALTHY NON-DIABETIC FEMALES, DUE TO GESTATIONAL INSULIN RESISTANCE THAT LEADS TO INCREASED BLOOD SUGAR LEVELS AND HYPERINSULINEMIA (INCREASED INSULIN PRODUCTION FROM THE PANCREATIC BETA CELLS). THE HYPOTHESIS STATES THAT UNNOTICED AND CONSTANT EXPOSURE TO THIS ENVIRONMENTAL CHEMICAL MIGHT POTENTIALLY LEAD TO THE FORMATION OF CHRONIC LOW-LEVEL ENDOCRINE DISRUPTIVE STATE THAT RESEMBLES GESTATIONAL INSULIN RESISTANCE, WHICH MIGHT CONTRIBUTE TO THE DEVELOPMENT OF DIABETES. THE INCREASING BODY OF EVIDENCE SUPPORTS THE MAJOR PREMISES OF THIS HYPOTHESIS, AS EXEMPLIFIED BY THE NUMEROUS PUBLICATIONS EXAMINING THE ASSOCIATION OF BPA AND INSULIN RESISTANCE, BOTH EPIDEMIOLOGICAL AND MECHANISTIC. HOWEVER, TO WHAT EXTENT BPA MIGHT CONTRIBUTE TO THE DEVELOPMENT OF DIABETES IN THE MODERN SOCIETIES STILL REMAINS UNKNOWN. IN THIS REVIEW, I DISCUSS THE CHEMICAL PROPERTIES OF BPA AND THE SOURCES OF BPA CONTAMINATION FOUND IN THE ENVIRONMENT AND IN HUMAN TISSUES. I PROVIDE AN OVERVIEW OF MECHANISMS FOR THE PROPOSED ROLE OF BISPHENOL A IN INSULIN RESISTANCE AND DIABETES, AS WELL AS OTHER RELATED DISEASES, SUCH AS CARDIOVASCULAR DISEASES. I DESCRIBE THE TRANSMISSION OF BPA EFFECTS TO THE OFFSPRING AND POSTULATE THAT GENDER RELATED DIFFERENCES MIGHT ORIGINATE FROM DIFFERENCES IN LIVER ENZYME LEVELS, SUCH AS UDP-GLUCURONOSYLTRANSFERASE, WHICH IS INVOLVED IN BPA PROCESSING AND ITS ELIMINATION FROM THE ORGANISM. I DISCUSS THE MOLECULAR MECHANISMS OF BPA ACTION THROUGH NUCLEAR AND MEMBRANE-BOUND ER RECEPTORS, NON-MONOTONIC DOSE RESPONSE, EPIGENETIC MODIFICATIONS OF THE DNA AND PROPOSE THAT CHRONIC EXPOSURE TO WEAK BINDERS, SUCH AS BPA, MAY MIMIC THE EFFECTS OF STRONG BINDERS, SUCH AS ESTROGENS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
3  4341  48 MIGRATION TEST OF BISPHENOL A FROM POLYCARBONATE CUPS USING EXCITATION-EMISSION FLUORESCENCE DATA WITH PARALLEL FACTOR ANALYSIS. BISPHENOL A (BPA) IS ONE OF THE MOST LARGELY PRODUCED CHEMICAL IN THE WORLD; IT IS USED TO MAKE PLASTICS AND EPOXY RESINS. THE ENDOCRINE DISRUPTOR POTENTIAL OF BPA IS WELL KNOWN, BUT RECENT RESEARCHES SUGGEST A RELATIONSHIP BETWEEN CHRONIC EXPOSURE TO BPA, GENOTOXIC ACTIVITY AND EPIGENETIC MODIFICATIONS. THE MAIN SOURCE OF EXPOSURE TO BPA INCLUDES FOOD CONTACT MATERIALS (FCM). THUS SIMPLE AND ROBUST TEST METHODS ARE NEEDED TO IMPROVE THE MIGRATION TEST OF BPA. IN THIS WORK, A NON-SEPARATIVE, EASY, FAST AND INEXPENSIVE SPECTROFLUORIMETRIC METHOD BASED ON THE SECOND ORDER CALIBRATION OF EXCITATION-EMISSION FLUORESCENCE MATRICES (EEMS) WAS PROPOSED FOR THE DETERMINATION OF BPA. FOR THE FIRST TIME, MOLECULAR FLUORESCENCE WAS USED TO IDENTIFY UNEQUIVOCALLY AND QUANTIFY BPA. TRILINEARITY OF THE DATA TENSOR GUARANTEES THE UNIQUENESS OF THE SOLUTION OBTAINED THROUGH PARALLEL FACTOR ANALYSIS (PARAFAC), SO ONE FACTOR OF THE DECOMPOSITION MATCHES UP WITH BPA EVEN IF OTHER FLUOROPHORES ARE IN THE TEST SAMPLE. THE EFFECT OF FOUR EXPERIMENTAL FACTORS OF THE PROCEDURE ON THE FIGURES OF MERIT AND THE UNEQUIVOCALLY IDENTIFICATION WAS INVESTIGATED BY MEANS OF A D-OPTIMAL DESIGN AND PARAFAC CALIBRATION. THE METHOD IS LINEAR AND ACCURATE IN THE RANGE 0-720MICROGL(-1). THE DECISION LIMIT CCALPHA AND DETECTION CAPABILITY CCBETA ARE 6.63MICROGL(-1) AND 18.85MICROGL(-1) RESPECTIVELY (WITH PROBABILITIES OF FALSE POSITIVE AND FALSE NEGATIVE FIXED AT 0.05). FINALLY THE PROPOSED METHOD WAS APPLIED TO CARRY OUT A MIGRATION TEST FROM TWO POLYCARBONATE CUPS, USING 3% (W/V) ACETIC ACID IN AQUEOUS SOLUTION AS FOOD SIMULANT. THE MIGRATED AMOUNT OF BPA WAS FOUND TO BE 688.7MICROGL(-1) (N=5) FOR THE FIRST CUP AND 710.5MICROGL(-1) (N=4) FOR THE SECOND ONE, ABOVE THE SPECIFIC MIGRATION LIMIT SET BY EFSA (EUROPEAN FOOD SAFETY AUTHORITY).	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
4    73  49 A MULTI-GENERATIONAL STUDY ON LOW-DOSE BPA EXPOSURE IN WISTAR RATS: EFFECTS ON MATERNAL BEHAVIOR, FLAVOR INTAKE AND DEVELOPMENT. BISPHENOL A (BPA) IS A COMMON ENDOCRINE DISRUPTOR FOUND AS AN ENVIRONMENTAL AND FOOD CONTAMINANT. IT EXERTS BOTH DEVELOPMENTAL AND BEHAVIORAL EFFECTS, MAINLY WHEN EXPOSURE OCCURS IN EARLY LIFE. THE AIM OF THIS STUDY WAS TO DETERMINE THE MULTI-GENERATIONAL EFFECTS OF CHRONIC, HUMAN-RELEVANT LOW-DOSE EXPOSURE TO BPA ON DEVELOPMENT, MATERNAL BEHAVIOR AND FLAVOR PREFERENCE IN WISTAR RATS. BPA WAS ORALLY ADMINISTERED AT A DAILY DOSE OF 5 MUG/KG BODY WEIGHT TO F0 PREGNANT DAMS FROM THE FIRST DAY OF GESTATION (GD 1) UNTIL THE LAST DAY OF LACTATION (LD 21), AND THEN TO F1 OFFSPRING FROM WEANING (PND 21) TO ADULTHOOD (PND 100). F2 OFFSPRING WERE NOT EXPOSED. DEVELOPMENT AND CLINICAL SIGNS OF TOXICITY WERE ASSESSED DAILY. MATERNAL BEHAVIOR WAS EVALUATED BY OBSERVING NURSING AND PUP-CARING ACTIONS, AS WELL AS "NON-MATERNAL" BEHAVIORS IN F0 AND F1 DAMS FROM PARTURITION UNTIL LD 8. THE FLAVOR PREFERENCES OF F1 AND F2 OFFSPRING WERE EVALUATED BASED ON THE INTAKE OF SWEET, SALT AND FAT SOLUTIONS USING THE TWO-BOTTLE CHOICE TEST ON PND 21-34 AND PND 86-99. BPA EXPOSURE: 1) DECREASED MATERNAL BEHAVIOR IN F1 DAMS, 2) CAUSED DEVELOPMENTAL DEFECTS IN BOTH F1 AND F2 OFFSPRING, WITH A NOTICEABLE DECREASE IN ANOGENITAL DISTANCE IN MALE RATS, AND 3) DID NOT AFFECT FLAVORED SOLUTION INTAKE IN F1, BUT INDUCED CHANGES IN SWEET PREFERENCE IN F2 JUVENILES AND IN SALT AND FAT SOLUTION INTAKES IN F2 ADULTS, AND 4) INDUCED A BODY WEIGHT INCREASE IN THE F2 GENERATION ONLY, WHEREAS FOOD INTAKE AND WATER CONSUMPTION DID NOT CHANGE. TAKEN AS A WHOLE, OUR FINDINGS SHOWED THAT BOTH GESTATIONAL (F0) AND LIFELONG (F1) EXPOSURES TO A HUMAN-RELEVANT DOSE OF BPA COULD INDUCE MULTI-GENERATIONAL EFFECTS ON BOTH DEVELOPMENT AND BEHAVIOR. THESE RESULTS SUGGEST POSSIBLE SELECTIVE NEUROENDOCRINE DEFECTS AND/OR EPIGENETIC CHANGES CAUSED BY BPA EXPOSURE.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
5   653  31 BISPHENOL A, HYPERTENSION, AND CARDIOVASCULAR DISEASES: EPIDEMIOLOGICAL, LABORATORY, AND CLINICAL TRIAL EVIDENCE. BISPHENOL A (BPA) EXPOSURE HAS BECOME ONE OF THE MOST COMMON ENVIRONMENTAL CHEMICAL EXPOSURES IN HUMANS. THERE IS GROWING EVIDENCE REGARDING AN ASSOCIATION BETWEEN BPA EXPOSURE, HYPERTENSION, AND CARDIOVASCULAR DISEASES (CVD). IF BPA EXPOSURE IS INDEED ASSOCIATED WITH RAISED BLOOD PRESSURE AND CVD, IT WOULD BE A MAJOR PUBLIC HEALTH PROBLEM. THEREFORE, WE REVIEWED THE EPIDEMIOLOGICAL, LABORATORY, AND CLINICAL TRIAL EVIDENCE FOR AN ASSOCIATION BETWEEN BPA EXPOSURE, CVD, AND HYPERTENSION, AND DISCUSSED THE POSSIBLE MECHANISMS IN THIS ARTICLE. CROSS-SECTIONAL STUDIES IN VARIOUS ETHNICITIES SUGGESTED A POSSIBLE ASSOCIATION BETWEEN BPA EXPOSURE AND HYPERTENSION; THIS ASSOCIATION WAS SUPPORTED BY A PANEL STUDY AND A RANDOMIZED CLINICAL TRIAL. DESPITE THE DISCORDANCE AMONG CROSS-SECTIONAL STUDIES ABOUT AN ASSOCIATION BETWEEN BPA EXPOSURE AND CVD, A LONGITUDINAL STUDY SHOWS THAT BPA EXPOSURE IS A RISK FACTOR FOR CVD. THE EFFECTS OF BPA EXPOSURE SUCH AS ENDOCRINAL DISTURBANCE, INDUCTION OF OXIDATIVE STRESS AND INFLAMMATION, EPIGENETIC CHANGE, AND LINKS WITH OTHER CHRONIC DISEASES MAY HIGHLIGHT A POSSIBLE MECHANISM BETWEEN BPA EXPOSURE, CVD, AND HYPERTENSION. TO CLARIFY THE CAUSAL RELATIONSHIP, WELL-DESIGNED STUDIES ARE NEEDED IN THE FUTURE.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
6  4015  47 LOW-DOSE EXPOSURE TO BISPHENOLS A, F AND S OF HUMAN PRIMARY ADIPOCYTE IMPACTS CODING AND NON-CODING RNA PROFILES. BISPHENOL A (BPA) EXPOSURE HAS BEEN SUSPECTED TO BE ASSOCIATED WITH DELETERIOUS EFFECTS ON HEALTH INCLUDING OBESITY AND METABOLICALLY-LINKED DISEASES. ALTHOUGH BISPHENOLS F (BPF) AND S (BPS) ARE BPA STRUCTURAL ANALOGS COMMONLY USED IN MANY MARKETED PRODUCTS AS A REPLACEMENT FOR BPA, ONLY SPARSE TOXICOLOGICAL DATA ARE AVAILABLE YET. OUR OBJECTIVE WAS TO COMPREHENSIVELY CHARACTERIZE BISPHENOLS GENE TARGETS IN A HUMAN PRIMARY ADIPOCYTE MODEL, IN ORDER TO DETERMINE WHETHER THEY MAY INDUCE CELLULAR DYSFUNCTION, USING CHRONIC EXPOSURE AT TWO CONCENTRATIONS: A "LOW-DOSE" SIMILAR TO THE DOSE USUALLY ENCOUNTERED IN HUMAN BIOLOGICAL FLUIDS AND A HIGHER DOSE. THEREFORE, BPA, BPF AND BPS HAVE BEEN ADDED AT 10 NM OR 10 MUM DURING THE DIFFERENTIATION OF HUMAN PRIMARY ADIPOCYTES FROM SUBCUTANEOUS FAT OF THREE NON-DIABETIC CAUCASIAN FEMALE PATIENTS. GENE EXPRESSION (MRNA/LNCRNA) ARRAYS AND MICRORNA ARRAYS, HAVE BEEN USED TO ASSESS CODING AND NON-CODING RNA CHANGES. WE DETECTED SIGNIFICANTLY DEREGULATED MRNA/LNCRNA AND MIRNA AT LOW AND HIGH DOSES. ENRICHMENT IN "CANCER" AND "ORGANISMAL INJURY AND ABNORMALITIES" RELATED PATHWAYS WAS FOUND IN RESPONSE TO THE THREE PRODUCTS. SOME LONG INTERGENIC NON-CODING RNAS AND SMALL NUCLEOLAR RNAS WERE DIFFERENTIALLY EXPRESSED SUGGESTING THAT BISPHENOLS MAY ALSO ACTIVATE MULTIPLE CELLULAR PROCESSES AND EPIGENETIC MODIFICATIONS. THE ANALYSIS OF UPSTREAM REGULATORS OF DEREGULATED GENES HIGHLIGHTED HORMONES OR HORMONE-LIKE CHEMICALS SUGGESTING THAT BPS AND BPF CAN BE SUSPECTED TO INTERFERE, JUST LIKE BPA, WITH HORMONAL REGULATION AND HAVE TO BE CONSIDERED AS ENDOCRINE DISRUPTORS. ALL THESE RESULTS SUGGEST THAT AS BPA, ITS SUBSTITUTES BPS AND BPF SHOULD BE USED WITH THE SAME RESTRICTIONS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
7  3304  87 HIGH-GLUCOSE CONCENTRATIONS CHANGE DNA METHYLATION LEVELS IN HUMAN IVM OOCYTES. STUDY QUESTION: WHAT ARE THE EFFECTS OF HIGH-GLUCOSE CONCENTRATIONS ON DNA METHYLATION OF HUMAN OOCYTES? SUMMARY ANSWER: HIGH-GLUCOSE CONCENTRATIONS ALTERED DNA METHYLATION LEVELS OF PEG3 AND ADIPONECTIN IN HUMAN IN VITRO MATURATION OOCYTES. WHAT IS KNOWN ALREADY: MATERNAL DIABETES HAS A DETRIMENTAL INFLUENCE ON OOCYTE QUALITY INCLUDING EPIGENETIC MODIFICATIONS, AS SHOWN IN NON-HUMAN MAMMALIAN SPECIES. STUDY DESIGN, SIZE, DURATION: IMMATURE METAPHASE I (MI) STAGE OOCYTES OF GOOD QUALITY WERE RETRIEVED FROM PATIENTS WHO HAD NORMAL OVARIAN POTENTIAL AND WHO UNDERWENT ICSI IN THE REPRODUCTIVE MEDICINE CENTER OF PEOPLE'S HOSPITAL OF ZHENGZHOU UNIVERSITY. MI OOCYTES WERE CULTURED IN MEDIUM WITH DIFFERENT GLUCOSE CONCENTRATIONS (CONTROL, 10 MM AND 15 MM) IN VITRO AND 48 H LATER, OOCYTES WITH FIRST POLAR BODY EXTRUSION WERE COLLECTED TO CHECK THE DNA METHYLATION LEVELS. PARTICIPANTS/MATERIALS, SETTING, METHODS: MI OOCYTES UNDERWENT IN VITRO MATURATION (IVM) AT 37 DEGREES C WITH 5% MIXED GAS FOR 48 H. THEN THE MATURE OOCYTES WERE TREATED WITH BISULFITE BUFFER. TARGET SEQUENCES WERE AMPLIFIED USING NESTED OR HALF-NESTED PCR AND THE DNA METHYLATION STATUS WAS TESTED USING COMBINED BISULFITE RESTRICTION ANALYSIS (COBRA) AND BISULFITE SEQUENCING (BS). MAIN RESULTS AND THE ROLE OF CHANCE: HIGH-GLUCOSE CONCENTRATIONS SIGNIFICANTLY DECREASED THE FIRST POLAR BODY EXTRUSION RATE. COMPARED TO CONTROLS, THE DNA METHYLATION LEVELS OF PEG3 IN HUMAN IVM OOCYTES WERE SIGNIFICANTLY HIGHER IN 10 MM (P < 0.001) AND 15 MM (P < 0.001) CONCENTRATIONS OF GLUCOSE. BUT THE DNA METHYLATION LEVEL OF H19 WAS NOT AFFECTED BY HIGH-GLUCOSE CONCENTRATIONS IN HUMAN IVM OOCYTES. WE ALSO FOUND THAT THERE WAS A DECREASE IN DNA METHYLATION LEVELS IN THE PROMOTER OF ADIPONECTIN IN HUMAN IVM OOCYTES BETWEEN CONTROLS AND OOCYTES EXPOSED TO 10 MM GLUCOSE (P = 0.028). LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: IT IS NOT CLEAR WHETHER THE ALTERATIONS ARE BENEFICIAL OR NOT FOR THE EMBRYO DEVELOPMENT AND OFFSPRING HEALTH. THE EFFECTS OF HIGH-GLUCOSE CONCENTRATIONS ON THE WHOLE PROCESS OF OOCYTE MATURATION ARE STILL NOT ELUCIDATED. ANOTHER ISSUE IS THAT THE NUMBER OF OOCYTES USED IN THIS STUDY WAS LIMITED. WIDER IMPLICATIONS OF THE FINDINGS: THIS IS THE FIRST TIME THAT THE EFFECTS OF HIGH-GLUCOSE CONCENTRATION ON DNA METHYLATION OF HUMAN OOCYTES HAVE BEEN ELUCIDATED. OUR RESULT INDICATES THAT IN HUMANS, THE HIGH RISK OF CHRONIC DISEASES IN OFFSPRING FROM DIABETIC MOTHERS MAY ORIGINATE FROM ABNORMAL DNA MODIFICATIONS IN OOCYTES. STUDY FUNDING/COMPETING INTEREST(S): THIS WORK WAS SUPPORTED BY THE FUND OF NATIONAL NATURAL SCIENCE FOUNDATION OF CHINA (81401198) AND DOCTOR FOUNDATION OF QINGDAO AGRICULTURAL UNIVERSITY (1116008).THE AUTHORS DECLARE THAT THERE ARE NO POTENTIAL CONFLICTS OF INTEREST RELEVANT TO THIS ARTICLE.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
8   745  97 CANNABIS ALTERS EPIGENETIC INTEGRITY AND ENDOCANNABINOID SIGNALLING IN THE HUMAN FOLLICULAR NICHE. STUDY QUESTION: DO PHYTOCANNABINOIDS (PCS) AFFECT FOLLICULAR ENDOCANNABINOID SIGNALLING AND THE EPIGENOME IN THE SURROUNDING GRANULOSA CELLS (GCS)? SUMMARY ANSWER: EXPOSURE TO PCS INCREASES THE EXPRESSION OF ENDOCANNABINOID RECEPTORS AND REDUCES DNA METHYLATION ENZYME EXPRESSION AND GLOBAL DNA METHYLATION IN NAIVE GCS. WHAT IS KNOWN ALREADY: CANNABIS PLANT DERIVATIVES, KNOWN AS PCS, ARE USED FOR MEDICINAL AND RECREATIONAL PURPOSES. THE MAIN PC, TETRAHYDROCANNABINOL (THC), IS THE THIRD MOST COMMONLY USED SUBSTANCE BY WOMEN OF CHILDBEARING AGE, HENCE KNOWLEDGE OF THE EFFECT IT HAS ON REPRODUCTION IS OF UTMOST IMPORTANCE. THC EXERTS ITS EFFECTS VIA RECEPTORS OF THE ENDOCANNABINOID SYSTEM (ECS) AND CAN INTERFERE WITH FOLLICULOGENESIS, OOCYTE DEVELOPMENT AND OVULATION. ENDOCANNABINOIDS HAVE BEEN MEASURED IN FOLLICULAR FLUID (FF) OBTAINED DURING OOCYTE RETRIEVAL AND ARE IMPLICATED IN CONTROLLING FOLLICULOGENESIS. IT HAS BEEN ESTABLISHED THAT IN THE PLACENTA, PCS DISRUPT ENDOCANNABINOID HOMEOSTASIS VIA IMPAIRMENT OF THE SYNTHETIC AND DEGRADING ENZYMES, LEADING TO A NET INCREASE OF ENDOCANNABINOID LEVELS. FINALLY, PREVIOUS STUDIES HAVE SHOWN THAT THC ALTERS METHYLATION AND HISTONE MODIFICATIONS IN SPERM, BRAIN AND BLOOD CELLS. STUDY DESIGN, SIZE, DURATION: THIS STUDY INCLUDED AN IN VIVO COHORT ASSESSMENT OF CANNABIS EXPOSURE AND ITS EFFECTS ON THE FOLLICLE AND IN VITRO ASSAYS CONDUCTED TO VALIDATE THE IN VIVO FINDINGS AND TO EXPLORE POSSIBLE MECHANISMS OF ACTION. PARTICIPANTS/MATERIALS, SETTING, METHODS: A TOTAL OF 318 FF SAMPLES, FROM 261 PATIENTS UNDERGOING IVF TREATMENT AT A PRIVATE FERTILITY CLINIC WHO CONSENTED FOR BIOBANKING BIOLOGICAL WASTE MATERIAL BETWEEN JANUARY 2018 AND JULY 2019, WERE INCLUDED IN THIS STUDY. CONCENTRATIONS OF PCS AND ENDOCANNABINOIDS WERE ASSESSED IN FF BY LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY (LC-MS/MS). EXPOSURE TO PCS WAS DETERMINED BASED ON THESE MEASURED LEVELS. LEVELS OF BOTH ENDOCANNABINOID RECEPTORS (CB1R, CB2R) AND THE DE NOVO DNA METHYLATING ENZYME, DNMT3B, IN GCS WERE ASSESSED BY FLOW CYTOMETRY BOTH IN VITRO AND IN VIVO AND GLOBAL DNA METHYLATION WAS ASSESSED IN VITRO BY ELISA. IN VIVO EFFECTS WERE ASSESSED BY COMPARING SAMPLES POSITIVE FOR AT LEAST ONE PC, WITH SAMPLES NEGATIVE FOR ALL MEASURED PCS. IN VITRO EFFECTS WERE DETERMINED IN NAIVE GCS, OBTAINED CONCURRENTLY WITH FF SAMPLES THAT HAD TESTED NEGATIVE FOR ALL PCS. THESE GCS WERE TREATED WITH DIFFERENT COMBINATIONS OF THE MAIN THREE PCS. MAIN RESULTS AND THE ROLE OF CHANCE: OVERALL, 17 PATIENTS (6.4%) WERE POSITIVE FOR CANNABIS CONSUMPTION. FURTHERMORE, THE PREVALENCE OF CANNABIS POSITIVITY IN THE FF INCREASED FROM 4% OF THE TESTED SAMPLES THAT WERE COLLECTED PRIOR TO NATIONAL LEGALISATION IN OCTOBER 2018 TO 12% OF THOSE COLLECTED FOLLOWING LEGALISATION. OF NOTE, 59% OF PATIENTS WHO TESTED POSITIVE FOR PCS (10 OF 17) REPORTED PREVIOUS OR ONGOING EXPOSURE TO CANNABIS UPON THEIR INITIAL INTAKE. ENDOCANNABINOID LEVELS WERE NOT AFFECTED BY THE PRESENCE OF PCS. CB2R WAS MORE PREVALENT THAN CB1R IN GCS AND ITS EXPRESSION INCREASED FOLLOWING ACUTE AND CHRONIC IN VITRO EXPOSURE TO PCS. THE EXPRESSION OF DNMT3B AND GLOBAL METHYLATION DECREASED FOLLOWING EXPOSURE, SUGGESTING THAT CANNABIS MAY AFFECT THE EPIGENOME IN THE FOLLICULAR NICHE. THE ACUTE CHANGES WERE SUSTAINED THROUGHOUT CHRONIC TREATMENT. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: OUR STUDY IS LIMITED BY LACK OF DETAILS REGARDING MODE, FREQUENCY AND TIMING OF PC CONSUMPTION. MOREOVER, WE WERE NOT ABLE TO ADEQUATELY ASSESS THE EFFECT OF PCS ON IMMEDIATE OR LONG-TERM CLINICAL OUTCOMES, DUE TO THE SMALL SAMPLE SIZE AND THE LACK OF FOLLOW UP. FUTURE, LARGE-SCALE STUDIES SHOULD FOCUS ON ASSESS THE CLINICAL IMPLICATIONS OF CANNABIS EXPOSURE, VALIDATE OUR FINDINGS, AND DETERMINE TO WHAT EXTENT CANNABIS AFFECTS THE EPIGENOME OVARIAN FOLLICLE AND THE DEVELOPING OOCYTE. WIDER IMPLICATIONS OF THE FINDINGS: TO OUR KNOWLEDGE, THIS IS THE FIRST STUDY MEASURING PCS IN FF BY LC-MS/MS. WE SHOW THAT CONSUMING CANNABIS ALTERS THE ECS IN THE DEVELOPING FOLLICLE, AND DIRECTLY AFFECTS DNMT EXPRESSION AND GLOBAL DNA METHYLATION LEVELS. CANNABIS LEGALISATION AND USE IS INCREASING WORLDWIDE, THEREFORE FURTHER UNDERSTANDING ITS ROLE IN FEMALE FERTILITY AND FOLLICULOGENESIS IS CRITICAL. STUDY FUNDING/COMPETING INTEREST(S): ALL FUNDING WAS PROVIDED BY CREATE FERTILITY CENTRE THROUGH THE REINVESTMENT OF CLINICAL EARNINGS. THE AUTHORS DECLARE NO COMPETING INTERESTS.	2021	

9  5093  87 PLACENTAS FROM PREGNANCIES CONCEIVED BY IVF/ICSI HAVE A REDUCED DNA METHYLATION LEVEL AT THE H19 AND MEST DIFFERENTIALLY METHYLATED REGIONS. STUDY QUESTION: DOES IVF/ICSI HAVE AN EFFECT ON THE EPIGENETIC REGULATION OF THE HUMAN PLACENTA? SUMMARY ANSWER: WE FOUND A REDUCED DNA METHYLATION LEVEL AT THE H19 AND MEST DIFFERENTIALLY METHYLATED REGIONS (DMRS), AND AN INCREASED RNA EXPRESSION OF H19 IN PLACENTAS FROM PREGNANCIES CONCEIVED BY IVF/ICSI WHEN COMPARED WITH PLACENTAS FROM SPONTANEOUS CONCEPTION. WHAT IS KNOWN ALREADY: CHANGES IN FETAL ENVIRONMENT ARE ASSOCIATED WITH ADVERSE HEALTH OUTCOMES. THE PLACENTA IS PIVOTAL FOR INTRAUTERINE ENVIRONMENT. ANIMAL STUDIES SHOW THAT EPIGENETIC REGULATION PLAYS AN IMPORTANT ROLE IN THESE ENVIRONMENT-INDUCED PHENOTYPIC EFFECTS. ALSO, THE PREIMPLANTATION EMBRYO ENVIRONMENT AFFECTS BIRTHWEIGHT AS WELL AS THE RISK OF CHRONIC ADULT DISEASES. EPIGENETIC PROCESSES ARE SENSITIVE TO THE ENVIRONMENT, ESPECIALLY DURING THE PERIOD AROUND CONCEPTION. STUDY DESIGN AND PARTICIPANTS: PLACENTAL TISSUE WAS COLLECTED FROM 35 SPONTANEOUSLY CONCEIVED PREGNANCIES AND 35 IVF/ICSI (5 IVF, 30 ICSI) DERIVED PREGNANCIES. WE QUANTITATIVELY ANALYSED THE DNA METHYLATION PATTERNS OF A NUMBER OF CONSECUTIVE CPGS IN THE CORE REGIONS OF DMRS AND OTHER REGULATORY REGIONS OF IMPRINTED GENES, SINCE THESE ARE INVOLVED IN PLACENTAL AND FETAL GROWTH AND DEVELOPMENT. METHODS: BY USING PYROSEQUENCING, THE DNA METHYLATION AT SEVEN GERMLINE-DERIVED PRIMARY DMRS WAS ANALYSED QUANTITATIVELY. FIVE OF THESE ARE MATERNALLY METHYLATED (MEST ISOFORM ALPHA AND BETA, PEG3, KCNQ1OT1 AND SNRPN) AND TWO ARE PATERNALLY METHYLATED [H19 DMR AND THE INTERGENIC REGION BETWEEN DLK1 AND MEG3 (IG-DMR)]. THE POST-FERTILIZATION-DERIVED SECONDARY DMRS, IGF2 (DMR0 AND 2) AND IG-DMR (CG7, ALSO CALLED MEG3 DMR), AND THE MEG3 PROMOTER REGION WERE EXAMINED AS WELL. IN CASE OF DIFFERENTIAL METHYLATION BETWEEN THE TWO GROUPS, THE EFFECT ON GENE EXPRESSION WAS ASSESSED BY QUANTITATIVE REAL-TIME PCR. MAIN RESULTS AND THE ROLE OF CHANCE: BOTH THE PROMOTER REGION OF MEST ISOFORM ALPHA AND BETA AND THE 6TH CTCF BINDING SITE WITHIN THE H19 DMR WERE SIGNIFICANTLY HYPOMETHYLATED IN THE IVF/ICSI GROUP. THE PHENOMENON WAS CONSISTENTLY OBSERVED OVER ALL CPG SITES ANALYSED AND NOT RESTRICTED TO SINGLE CPG SITES. THE OTHER PRIMARY AND SECONDARY DMRS WERE NOT AFFECTED. EXPRESSION OF H19 WAS INCREASED IN THE IVF/ICSI GROUP, WHILE THAT OF IGF2 AND MEST REMAINED SIMILAR. LIMITATIONS, REASONS FOR CAUTION: IN THE IVF/ICSI GROUP, MOSTLY ICSI PREGNANCIES WERE INVESTIGATED. THE ICSI TECHNIQUE OR MALE SUBFERTILITY COULD BE A CONFOUNDING FACTOR. THEREFORE, OUR RESULTS ARE LESS GENERALIZABLE TO IVF PREGNANCIES. WIDER IMPLICATIONS OF THE FINDINGS: THE CLINICAL EFFECTS OF THE OBSERVED PLACENTAL HYPOMETHYLATIONS ON THE DEVELOPMENTAL PROGRAMMING OF THE IVF/ICSI PROGENY, IF ANY, ARE AS YET UNKNOWN. WHETHER THE HYPOMETHYLATION IS AN ADAPTATION OF THE PLACENTA TO MAINTAIN FETAL SUPPLY AND AMELIORATE THE EFFECTS OF ENVIRONMENTAL CUES, OR WHETHER IT IS A DEREGULATION LEADING TO DERANGED DEVELOPMENTAL PROGRAMMING WITH OR WITHOUT INCREASED VULNERABILITY FOR DISEASE, CONSISTENT WITH THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE HYPOTHESIS, NEEDS FURTHER INVESTIGATION. STUDY FUNDING/COMPETING INTEREST(S): PARTLY FUNDED BY AN UNRESTRICTED RESEARCH GRANT BY ORGANON BV (NOW MSD BV) WITHOUT ANY ROLE IN STUDY DESIGN, DATA COLLECTION AND ANALYSIS, OR PREPARATION OF THE MANUSCRIPT. NO CONFLICT OF INTERESTS TO DECLARE. TRIAL REGISTRATION NUMBER: DUTCH TRIAL REGISTRY (NTR) NUMBER 1298.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
10  3179  53 HAIR CORTISOL AS A HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BIOMARKER IN PREGNANT WOMEN WITH ASTHMA: A RETROSPECTIVE OBSERVATIONAL STUDY. BACKGROUND: CORTISOL IS A HORMONE INVOLVED IN MANY PHYSIOLOGICAL FUNCTIONS INCLUDING FETAL MATURATION AND EPIGENETIC PROGRAMMING DURING PREGNANCY. THIS STUDY AIMED TO USE HAIR CORTISOL AS A BIOMARKER OF CHRONIC INHALED CORTICOSTEROID (ICS) EXPOSURE AND ASSESS THE POTENTIAL EFFECTS OF ASTHMA ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN PREGNANT WOMEN. WE HYPOTHESIZED THAT PREGNANT WOMEN WITH ASTHMA TREATED WITH ICS WOULD EXHIBIT LOWER HAIR CORTISOL CONCENTRATIONS, INDICATIVE OF ADRENAL SUPPRESSION, COMPARED TO WOMEN WITH ASTHMA NOT USING ICS AND WOMEN WHO DO NOT HAVE ASTHMA. METHODS: WE PERFORMED AN OBSERVATIONAL RETROSPECTIVE COHORT STUDY. HAIR SAMPLES WERE ANALYZED FROM PREGNANT WOMEN WITH ASTHMA, WITH (N = 56) AND WITHOUT (N = 31) ICS TREATMENT, AND PREGNANT WOMEN WITHOUT ASTHMA (N = 31). HAIR SAMPLES WERE SEGMENTED BASED ON THE GROWTH RATE OF 1 CM/MONTH AND ANALYZED BY ENZYME IMMUNOASSAY TO PROVIDE CORTISOL CONCENTRATIONS CORRESPONDING TO PRECONCEPTION, TRIMESTERS 1-3, AND POSTPARTUM. HAIR CORTISOL CONCENTRATIONS WERE COMPARED WITHIN AND AMONG THE GROUPS USING NON-PARAMETRIC STATISTICAL TESTS. RESULTS: HAIR CORTISOL CONCENTRATIONS INCREASED ACROSS TRIMESTERS FOR ALL THREE GROUPS, BUT THIS INCREASE WAS DAMPENED IN WOMEN WITH ASTHMA (P = 0.03 FOR CONTROLS VS. ICS TREATED AND CONTROLS VS. NO ICS). ICS TREATED WOMEN TAKING MORE THAN FIVE DOSES PER WEEK HAD HAIR CORTISOL CONCENTRATIONS 47 % LOWER IN THIRD TRIMESTER THAN CONTROLS. LINEAR REGRESSION OF THE THIRD TRIMESTER HAIR CORTISOL RESULTS IDENTIFIED ASTHMA AS A SIGNIFICANT FACTOR WHEN COMPARING CONSISTENT ICS USE OR ASTHMA AS THE PREDICTOR (F(1, 25) = 9.7, P = 0.005, R(2) ADJ = 0.257). CONCLUSIONS: HAIR CORTISOL SUCCESSFULLY SHOWED THE EXPECTED CHANGE IN CORTISOL OVER THE COURSE OF PREGNANCY AND MAY BE A USEFUL BIOMARKER OF HPA AXIS FUNCTION IN PREGNANT WOMEN WITH ASTHMA. THE POTENTIAL IMPACT OF DECREASED MATERNAL CORTISOL IN WOMEN WITH ASTHMA ON PERINATAL OUTCOMES REMAINS TO BE DETERMINED.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
11  1140  36 CONCENTRATION OF FOLIC ACID (FA) IN SERUM OF JAPANESE PREGNANT WOMEN. OBJECTIVES EXPOSURE TO INORGANIC ARSENIC (IAS) IS A WORLD-WIDE HEALTH CONCERN. WE REPORTED THAT JAPANESE CHILDREN AND PREGNANT WOMEN ARE EXPOSED TO MODERATE LEVELS OF IAS THROUGH FOOD. REDUCING IAS CONTAMINATION FROM FOODS OF HIGH IAS IS AN IMPORTANT ISSUE UNIQUE IN JAPAN. INTEGRATED IAS IS METHYLATED TO LESS TOXIC ORGANIC FORMS, AND S-ADENOSYL-L-METHYONINE (SAM), A COMMON METHYL-DONOR OF DNA AND HISTONES, IS UTILIZED IN THIS PROCESS. CHRONIC CONSUMPTION OF SAM BY IAS METABOLISM DUE TO EXPOSURE TO IAS MIGHT ALTER THE EPIGENETIC MODIFICATION OF GENOME. THE SAM BIOSYNTHESIS PATHWAY IS DEPENDENT ON FOLATE CYCLE, AND IT IS POSSIBLE THAT INGESTION OF SUFFICIENT FOLIC ACID (FA) IS PROTECTIVE TO IAS INDUCED TOXICITY. METHODS IN THE COURSE OF OUR CROSS-SECTIONAL BODY BURDEN ANALYSES OF PB AND IAS IN JAPANESE CHILDREN AND PREGNANT WOMEN, TERMED "PBAS STUDY", FA CONCENTRATION IN SERUM OF 104 PREGNANT WOMEN WAS MEASURED. RESULTS MEAN (+/-SEM) OF SERUM FA CONCENTRATION WAS 15.8 +/- 1.3 (NG/ML). THERE ARE SIGNIFICANT NUMBER OF PEOPLE SHOWING VERY HIGH FA (>30 NG/ ML), AND LARGE FRACTION OF THEM WERE TAKING SUPPLEMENTS DAILY. CONCLUSIONS THESE RESULTS SUGGESTED THAT LEVEL OF FA INGESTION OF JAPANESE PREGNANT WOMEN IS HIGH FOR SUPPORTING NORMAL FETAL DEVELOPMENT.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
12  2632  55 EPIGENOME-WIDE DNA METHYLATION AND PESTICIDE USE IN THE AGRICULTURAL LUNG HEALTH STUDY. BACKGROUND: PESTICIDE EXPOSURE IS ASSOCIATED WITH MANY LONG-TERM HEALTH OUTCOMES; THE POTENTIAL UNDERLYING MECHANISMS ARE NOT WELL ESTABLISHED FOR MOST ASSOCIATIONS. EPIGENETIC MODIFICATIONS, SUCH AS DNA METHYLATION, MAY CONTRIBUTE. INDIVIDUAL PESTICIDES MAY BE ASSOCIATED WITH SPECIFIC DNA METHYLATION PATTERNS BUT NO EPIGENOME-WIDE ASSOCIATION STUDY (EWAS) HAS EVALUATED METHYLATION IN RELATION TO INDIVIDUAL PESTICIDES. OBJECTIVES: WE CONDUCTED AN EWAS OF DNA METHYLATION IN RELATION TO SEVERAL PESTICIDE ACTIVE INGREDIENTS. METHODS: THE AGRICULTURAL LUNG HEALTH STUDY IS A CASE-CONTROL STUDY OF ASTHMA, NESTED WITHIN THE AGRICULTURAL HEALTH STUDY. WE ANALYZED BLOOD DNA METHYLATION MEASURED USING ILLUMINA'S EPIC ARRAY IN 1,170 MALE FARMERS OF EUROPEAN ANCESTRY. FOR PESTICIDES STILL ON THE MARKET AT BLOOD COLLECTION (2009-2013), WE EVALUATED NINE ACTIVE INGREDIENTS FOR WHICH AT LEAST 30 PARTICIPANTS REPORTED PAST AND CURRENT (WITHIN THE LAST 12 MONTHS) USE, AS WELL AS SEVEN BANNED ORGANOCHLORINES WITH AT LEAST 30 PARTICIPANTS REPORTING PAST USE. WE USED ROBUST LINEAR REGRESSION TO COMPARE METHYLATION AT INDIVIDUAL C-PHOSPHATE-G SITES (CPGS) AMONG USERS OF A SPECIFIC PESTICIDE TO NEVER USERS. RESULTS: USING FAMILY-WISE ERROR RATE (P < 9 X 10-8) OR FALSE-DISCOVERY RATE (FDR < 0.05), WE IDENTIFIED 162 DIFFERENTIALLY METHYLATED CPGS ACROSS 8 OF 9 CURRENTLY MARKETED ACTIVE INGREDIENTS (ACETOCHLOR, ATRAZINE, DICAMBA, GLYPHOSATE, MALATHION, METOLACHLOR, MESOTRIONE, AND PICLORAM) AND ONE BANNED ORGANOCHLORINE (HEPTACHLOR). DIFFERENTIALLY METHYLATED CPGS WERE UNIQUE TO EACH ACTIVE INGREDIENT, AND A DOSE-RESPONSE RELATIONSHIP WITH LIFETIME DAYS OF USE WAS OBSERVED FOR MOST. SIGNIFICANT CPGS WERE ENRICHED FOR TRANSCRIPTION MOTIFS AND 28% OF CPGS WERE ASSOCIATED WITH WHOLE BLOOD CIS-GENE EXPRESSION, SUPPORTING FUNCTIONAL EFFECTS OF FINDINGS. WE CORROBORATED A PREVIOUSLY REPORTED ASSOCIATION BETWEEN DICHLORODIPHENYLTRICHLOROETHANE (BANNED IN THE UNITED STATES IN 1972) AND EPIGENETIC AGE ACCELERATION. DISCUSSION: WE IDENTIFIED DIFFERENTIAL METHYLATION FOR SEVERAL ACTIVE INGREDIENTS IN MALE FARMERS OF EUROPEAN ANCESTRY. THESE MAY SERVE AS BIOMARKERS OF CHRONIC EXPOSURE AND COULD INFORM MECHANISMS OF LONG-TERM HEALTH OUTCOMES FROM PESTICIDE EXPOSURE. HTTPS://DOI.ORG/10.1289/EHP8928.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
13   518  41 ASSOCIATIONS BETWEEN ANTIBIOTIC EXPOSURE DURING PREGNANCY, BIRTH WEIGHT AND ABERRANT METHYLATION AT IMPRINTED GENES AMONG OFFSPRING. OBJECTIVES: LOW BIRTH WEIGHT (LBW) HAS BEEN ASSOCIATED WITH COMMON ADULT-ONSET CHRONIC DISEASES, INCLUDING OBESITY, CARDIOVASCULAR DISEASE, TYPE II DIABETES AND SOME CANCERS. THE ETIOLOGY OF LBW IS MULTI-FACTORIAL. HOWEVER, RECENT EVIDENCE SUGGESTS EXPOSURE TO ANTIBIOTICS MAY ALSO INCREASE THE RISK OF LBW. THE MECHANISMS UNDERLYING THIS ASSOCIATION ARE UNKNOWN, ALTHOUGH EPIGENETIC MECHANISMS ARE HYPOTHESIZED. IN THIS STUDY, WE EVALUATED THE ASSOCIATION BETWEEN MATERNAL ANTIBIOTIC USE AND LBW AND EXAMINED THE POTENTIAL ROLE OF ALTERED DNA METHYLATION THAT CONTROLS GROWTH REGULATORY IMPRINTED GENES IN THESE ASSOCIATIONS. METHODS: BETWEEN 2009-2011, 397 PREGNANT WOMEN WERE ENROLLED AND FOLLOWED UNTIL DELIVERY. PRENATAL ANTIBIOTIC USE WAS ASCERTAINED THROUGH MATERNAL SELF-REPORT. IMPRINTED GENES METHYLATION LEVELS WERE MEASURED AT DIFFERENTIALLY METHYLATED REGIONS (DMRS) USING BISULFITE PYROSEQUENCING. GENERALIZED LINEAR MODELS WERE USED TO EXAMINE ASSOCIATIONS AMONG ANTIBIOTIC USE, BIRTH WEIGHT AND DMR METHYLATION FRACTIONS. RESULTS: AFTER ADJUSTING FOR INFANT GENDER, RACE/ETHNICITY, MATERNAL BODY MASS INDEX, DELIVERY ROUTE, GESTATIONAL WEIGHT GAIN, GESTATIONAL AGE AT DELIVERY, FOLIC ACID INTAKE, PHYSICAL ACTIVITY, MATERNAL SMOKING AND PARITY, ANTIBIOTIC USE DURING PREGNANCY WAS ASSOCIATED WITH 138 G LOWER BIRTH WEIGHT COMPARED WITH NON-ANTIBIOTIC USE (BETA-COEFFICIENT=-132.99, S.E.=50.70, P=0.008). THESE ASSOCIATIONS WERE STRONGEST IN NEWBORNS OF WOMEN WHO REPORTED ANTIBIOTIC USE OTHER THAN PENICILLINS (BETA-COEFFICIENT=-135.57, S.E.=57.38, P=0.02). METHYLATION AT FIVE DMRS, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) AND PEG3 (P=0.08), WAS ASSOCIATED WITH MATERNAL ANTIBIOTIC USE; AMONG THESE, ONLY METHYLATION AT THE PLAGL1 DMR WAS ALSO ASSOCIATED WITH BIRTH WEIGHT. CONCLUSION: WE REPORT AN INVERSE ASSOCIATION BETWEEN IN UTERO EXPOSURE TO ANTIBIOTICS AND LOWER INFANT BIRTH WEIGHT AND PROVIDE THE FIRST EMPIRICAL EVIDENCE SUPPORTING IMPRINTED GENE PLASTICITY IN THESE ASSOCIATIONS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
14   899  37 CHRONIC EXPOSURE TO A LOW CONCENTRATION OF BISPHENOL A DURING FOLLICLE CULTURE AFFECTS THE EPIGENETIC STATUS OF GERMINAL VESICLES AND METAPHASE II OOCYTES. OBJECTIVE: TO DETERMINE WHETHER EXPOSURE TO LOW CONCENTRATIONS OF THE ENDOCRINE DISRUPTING CHEMICAL BISPHENOL A (BPA) DURING FOLLICLE CULTURE AND OOCYTE GROWTH ALTERS THE METHYLATION STATUS OF DIFFERENTIALLY METHYLATED REGIONS (DMRS) OF IMPRINTED GENES AND HISTONE POSTTRANSLATIONAL MODIFICATION PATTERNS IN MAMMALIAN OOCYTES. DESIGN: COMPARATIVE AND CONTROL STUDY. SETTING: EXPERIMENTAL LABORATORY. ANIMAL(S): C57/BL6JXCBA/CA MICE. INTERVENTION(S): EXPOSURE OF OOCYTES TO 3 NM OR 300 NM BPA DURING FOLLICLE CULTURE FROM PREANTRAL TO ANTRAL STAGE. MAIN OUTCOME MEASURE(S): METHYLATION STATUS OF DMRS OF MATERNALLY IMPRINTED (SNRPN, IGF2R, AND MEST) AND PATERNALLY IMPRINTED GENE(S) (H19) IN MOUSE GERMINAL VESICLE OOCYTES; TRIMETHYLATION OF HISTONE H3K9, ACETYLATION OF HISTONE H4K12, AND DISTANCE BETWEEN CENTROMERES OF SISTER CHROMATIDS IN METAPHASE II OOCYTES. RESULT(S): EXPOSURE TO 3 NM BPA WAS ASSOCIATED WITH SLIGHTLY ACCELERATED FOLLICLE DEVELOPMENT, STATISTICALLY SIGNIFICANT INCREASES IN ALLELE METHYLATION ERRORS IN DMRS OF MATERNALLY IMPRINTED GENES, AND STATISTICALLY SIGNIFICANT DECREASES IN HISTONE H3K9 TRIMETHYLATION AND INTERKINETOCHORE DISTANCE. CONCLUSION(S): THE DISTURBANCES IN OOCYTE GENOMIC IMPRINTING AND MODIFICATION OF POSTTRANSLATIONAL HISTONE AND CENTROMERE ARCHITECTURE PROVIDE THE FIRST LINK BETWEEN LOW BPA EXPOSURES AND INDUCTION OF EPIGENETIC CHANGES THAT MAY CONTRIBUTE TO CHROMOSOME CONGRESSION FAILURES AND MEIOTIC ERRORS, AND TO ALTERED GENE EXPRESSION THAT MIGHT AFFECT HEALTH OF THE OFFSPRING.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
15  6672  49 USE OF A MOUSE IN VITRO FERTILIZATION MODEL TO UNDERSTAND THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE HYPOTHESIS. THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE HYPOTHESIS HOLDS THAT ALTERATIONS TO HOMEOSTASIS DURING CRITICAL PERIODS OF DEVELOPMENT CAN PREDISPOSE INDIVIDUALS TO ADULT-ONSET CHRONIC DISEASES SUCH AS DIABETES AND METABOLIC SYNDROME. IT REMAINS CONTROVERSIAL WHETHER PREIMPLANTATION EMBRYO MANIPULATION, CLINICALLY USED TO TREAT PATIENTS WITH INFERTILITY, DISTURBS HOMEOSTASIS AND AFFECTS LONG-TERM GROWTH AND METABOLISM. TO ADDRESS THIS CONTROVERSY, WE HAVE ASSESSED THE EFFECTS OF IN VITRO FERTILIZATION (IVF) ON POSTNATAL PHYSIOLOGY IN MICE. WE DEMONSTRATE THAT IVF AND EMBRYO CULTURE, EVEN UNDER CONDITIONS CONSIDERED OPTIMAL FOR MOUSE EMBRYO CULTURE, ALTER POSTNATAL GROWTH TRAJECTORY, FAT ACCUMULATION, AND GLUCOSE METABOLISM IN ADULT MICE. UNBIASED METABOLIC PROFILING IN SERUM AND MICROARRAY ANALYSIS OF PANCREATIC ISLETS AND INSULIN SENSITIVE TISSUES (LIVER, SKELETAL MUSCLE, AND ADIPOSE TISSUE) REVEALED BROAD CHANGES IN METABOLIC HOMEOSTASIS, CHARACTERIZED BY SYSTEMIC OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION. ADOPTING A CANDIDATE APPROACH, WE IDENTIFY THIOREDOXIN-INTERACTING PROTEIN (TXNIP), A KEY MOLECULE INVOLVED IN INTEGRATING CELLULAR NUTRITIONAL AND OXIDATIVE STATES WITH METABOLIC RESPONSE, AS A MARKER FOR PREIMPLANTATION STRESS AND DEMONSTRATE TISSUE-SPECIFIC EPIGENETIC AND TRANSCRIPTIONAL TXNIP MISREGULATION IN SELECTED ADULT TISSUES. IMPORTANTLY, DYSREGULATION OF TXNIP EXPRESSION IS ASSOCIATED WITH ENRICHMENT FOR H4 ACETYLATION AT THE TXNIP PROMOTER THAT PERSISTS FROM THE BLASTOCYST STAGE THROUGH ADULTHOOD IN ADIPOSE TISSUE. OUR DATA SUPPORT THE VULNERABILITY OF PREIMPLANTATION EMBRYOS TO ENVIRONMENTAL DISTURBANCE AND DEMONSTRATE THAT CONCEPTION BY IVF CAN REPROGRAM METABOLIC HOMEOSTASIS THROUGH METABOLIC, TRANSCRIPTIONAL, AND EPIGENETIC MECHANISMS WITH LASTING EFFECTS FOR ADULT GROWTH AND FITNESS. THIS STUDY HAS WIDE CLINICAL RELEVANCE AND UNDERSCORES THE IMPORTANCE OF CONTINUED FOLLOW-UP OF IVF-CONCEIVED OFFSPRING.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
16   652  50 BISPHENOL A AS EPIGENETIC MODULATOR: SETTING THE STAGE FOR CARCINOGENESIS? BACKGROUND: BISPHENOL A (BPA) IS ONE OF THE MOST WIDELY PRODUCED CHEMICALS WORLDWIDE AND IS OFTEN USED IN THE PRODUCTION OF FOOD AND BEVERAGE CONTAINERS. AS A RESULT OF BPA CONTACT WITH FOOD, DRINK AND TOILETRIES, ITS INGESTION AND ABSORPTION BY HUMANS HAS BEEN GROWING. THE INDUSTRIALIZATION AND MODERN LIFESTYLES BROUGHT A CONSTANT EXPOSURE TO SEVERAL HEALTH-DISTURBING COMPOUNDS AND USHERED A NEW ERA OF CHRONIC DISEASES. THE ENDOCRINE DISRUPTOR POTENTIAL OF BPA IS WELL KNOWN, BUT THE RESEARCH AROUND ITS EPIGENOTOXIC EFFECTS RAISED FURTHER CONCERNS WHETHER CHRONIC EXPOSURE TO BPA CAN CONTRIBUTE TO CHRONIC HUMAN ILLNESS, INCLUDING CANCER IN HORMONE-SENSITIVE ORGANS. MATERIALS AND METHODS: FOCUSING ON COMPUTERIZED DATABASES, WE REVIEWED ORIGINAL AND REVIEW ARTICLES WHICH ELUCIDATE AND LINK SOME OF THE INFORMATION ALREADY AVAILABLE ABOUT BPA AND RELATED EPIGENETIC ALTERATIONS. RESULTS: A NUMBER OF STUDIES INDICATE THAT SHORT-TERM ADMINISTRATION OF LOW OR HIGH-DOSES OF BPA MAY BE ASSOCIATED WITH AN INCREASED RISK OF EPIGENETIC MODIFICATIONS, INCREASING THE RISK FOR CARCINOGENESIS. HOWEVER, IT IS CLEAR THAT MORE STUDIES CONSIDERING REAL DAILY EXPOSURES ARE ESSENTIAL TO DEFINE A REAL TOLERABLE DAILY INTAKE AND TO TIGHTEN UP MANUFACTORY REGULATIONS. CONCLUSION: IN THIS REVIEW, WE HIGHLIGHT SOME EVIDENCES SUGGESTING A RELATIONSHIP BETWEEN BPA EXPOSURE, GENOTOXIC ACTIVITY AND EPIGENETIC MODIFICATIONS, WHICH MAY PRIME FOR CARCINOGENESIS.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
17  3901  47 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
18  6084  48 THE EFFECT OF TRAINING ABOUT ENVIRONMENTAL TOXICANT BISPHENOL-A EXPOSURE IN PREGNANCY ON MATERNAL URINE BISPHENOL-A LEVEL. PURPOSE: BISPHENOL A (BPA) IS AN ENVIRONMENTAL TOXIN, CLEARLY CAPABLE OF INITIATING EPIGENETIC MODIFICATIONS, LEADING TO THE DEVELOPMENT OF NUMEROUS HUMAN ILLNESSES SUCH AS METABOLIC, REPRODUCTIVE, AND BEHAVIOURAL ABNORMALITIES. IT ALSO CAUSES OXIDATIVE STRESS, WHICH HAS BEEN SHOWN TO BE ALLEVIATED BY SELENIUM SUPPLEMENTATION. THE PURPOSE OF THIS STUDY WAS TO DETERMINE THE EFFECT OF TRAINING OF BPA EXPOSURE DURING PREGNANCY ON URINE BPA LEVELS. METHODS: THIS RESEARCH ENROLLED 30 PREGNANT WOMEN WHO WERE IN THEIR FIRST TRIMESTER AND WERE FREE OF CHRONIC ILLNESS. WOMEN WERE ASKED QUESTIONS ON THEIR SOCIODEMOGRAPHIC FEATURES, ANTHROPOMETRIC MEASURES, OBSTETRIC CHARACTERISTICS, BPA AWARENESS LEVEL, BPA EXPOSURE AND THE HEALTH PRACTICES IN PREGNANCY SCALE AS A PRE-TEST AND POST-TEST. THE INITIAL URINE SAMPLES WERE TAKEN FROM WOMEN IN THEIR FIRST TRIMESTER AND STORED IN BPA-FREE BAGS. THEN, TRAINING WAS DELIVERED TO ENCOURAGE BPA EXPOSURE REDUCTION AND MATERNAL HEALTH AWARENESS. FIRST-TRIMESTER FACE-TO-FACE INSTRUCTION AND BROCHURE DISTRIBUTION WERE FOLLOWED BY REFRESHER, REMINDER, AND FOLLOW-UP TRAININGS DURING THE SECOND AND THIRD TRIMESTERS. URINE SAMPLES FROM WOMEN IN THEIR SECOND AND THIRD TRIMESTERS WERE OBTAINED AGAIN. THE LEVELS OF BPA IN URINE WERE MEASURED USING THE LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY ON 90 SAMPLES. EACH PERSON'S URINE CONCENTRATION DIFFERS, THUS THE CREATININE LEVEL IN ALL SAMPLES WAS ALSO CALCULATED AND COMPARED TO THE BPA CONTENT, AND THE RESULTS WERE EVALUATED. RESULTS: OUR STUDY SHOWN THAT BPA EXPOSURE MAY BE LOWERED BY TRAINING. IT HAS BEEN DEMONSTRATED THAT REDUCING BPA EXPOSURE AND INCREASING KNOWLEDGE CAN RESULT IN AN IMPROVEMENT IN HEALTH STATUS. ADDITIONALLY, IT HAS BEEN DEMONSTRATED THAT TRAININGS GREATLY MINIMIZE EXPOSURE-CAUSING BEHAVIOURS. CONCLUSION: IT WAS DISCOVERED THAT WHILE THE DURATION OF A SINGLE TRAINING DOES NOT MAKE A MEANINGFUL EFFECT, THE CONTINUING OF REMINDER TRAININGS DID MAKE A SUBSTANTIAL DIFFERENCE IN THE URINE BPA LEVEL.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
19  1825  30 EFFECTS OF HIGH-DOSE BISPHENOL A ON THE MOUSE ORAL MUCOSA: A POSSIBLE LINK WITH ORAL CANCERS. BISPHENOL A (BPA) IS AN ENDOCRINE DISRUPTING CHEMICAL ABLE TO PROMOTE HORMONE-RESPONSIVE TUMORS. THE MAJOR ROUTE OF BPA CONTAMINATION BEING ORAL, THE AIM OF THE PRESENT STUDY WAS TO INVESTIGATE BPA EFFECTS ON ORAL CELLS. HERE, WE EVALUATED THE IMPACT OF SUB-CHRONIC IN VIVO EXPOSURE TO BPA AND ITS IN VITRO EFFECTS ON NEOPLASTIC AND NON-NEOPLASTIC ORAL CELLS. WE EVALUATED THE ORAL MUCOSA OF MICE CHRONICALLY EXPOSED TO BPA (200 MG/L). THE RESPONSE OF KERATINOCYTES (NOK-SI) AND HEAD AND NECK (HN) SQUAMOUS CELL CARCINOMA (SCC), HN12 AND HN13 CELL LINES TO BPA WAS EXAMINED. IN VIVO, BPA ACCUMULATED IN ORAL TISSUES AND CAUSED AN INCREASE IN EPITHELIAL PROLIFERATIVE ACTIVITY. BPA DISRUPTED THE FUNCTION OF KERATINOCYTES BY ALTERING PRO-SURVIVAL AND PROLIFERATIVE PATHWAYS AND THE SECRETION OF CYTOKINES AND GROWTH FACTORS. IN TUMOR CELLS, BPA INDUCED PROLIFERATIVE, INVASIVE, PRO-ANGIOGENIC, AND EPIGENETIC PATHS. OUR DATA HIGHLIGHT THE HARMFUL EFFECTS OF BPA ON ORAL MUCOSA AND, TUMORIGENIC AND NON-TUMORIGENIC CELLS. ADDITIONALLY, BPA MAY BE A MODIFIER OF ORAL CANCER CELL BEHAVIOR BY PROMPTING A FUNCTIONAL SHIFT TO A MORE AGGRESSIVE PHENOTYPE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
20  4066  34 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