1 6556 94 TRANSGENERATIONAL EFFECTS OF POLYETHYLENE MICROPLASTIC FRAGMENTS CONTAINING BENZOPHENONE-3 ADDITIVE IN DAPHNIA MAGNA. MATERNAL EXPOSURE TO MICROPLASTICS (MPS) PLAYS AN IMPORTANT ROLE IN THE FITNESS OF UNEXPOSED PROGENY. IN THIS STUDY, THE TRANSGENERATIONAL EFFECTS OF POLYETHYLENE MP FRAGMENTS (17.35 +/- 5.50 MICROM) CONTAINING BENZOPHENONE-3 (BP-3; 2.85 +/- 0.16% W/W) ON CHRONIC TOXICITY (21 D) IN DAPHNIA MAGNA WERE INVESTIGATED ACROSS FOUR GENERATIONS. ONLY D. MAGNA IN THE F0 GENERATION WAS EXPOSED TO MP FRAGMENTS, MP/BP-3 FRAGMENTS, AND BP-3 LEACHATE TO IDENTIFY THE TRANSGENERATIONAL EFFECT IN THE F3 GENERATION. THE MORTALITY OF D. MAGNA INDUCED BY MP AND MP/BP-3 FRAGMENTS WAS RECOVERED IN THE F3 GENERATION, BUT SOMATIC GROWTH AND REPRODUCTION SIGNIFICANTLY DECREASED COMPARED TO THE CONTROL. ADDITIONALLY, REPRODUCTION OF D. MAGNA EXPOSED TO BP-3 LEACHATE SIGNIFICANTLY DECREASED IN THE F3 GENERATION. THESE FINDINGS CONFIRMED THE TRANSGENERATIONAL EFFECTS OF MP FRAGMENT AND BP-3 ADDITIVE ON D. MAGNA. PARTICULARLY, THE ADVERSE EFFECT ON D. MAGNA REPRODUCTION SEEMED TO BE CUMULATIVE ACROSS FOUR GENERATIONS FOR MP/BP-3 FRAGMENTS, WHILE IT WAS AN ACCLIMATION TREND FOR BP-3 LEACHATE. HOWEVER, THERE WAS NO SIGNIFICANT DIFFERENCE IN GLOBAL DNA METHYLATION IN D. MAGNA ACROSS FOUR GENERATIONS, THUS REQUIRING A GENE-SPECIFIC DNA METHYLATION STUDY TO IDENTIFY DIFFERENT EPIGENETIC TRANSGENERATIONAL INHERITANCE. 2022 2 6552 35 TRANSGENERATIONAL DNA METHYLATION CHANGES IN DAPHNIA MAGNA EXPOSED TO CHRONIC GAMMA IRRADIATION. OUR AIM WAS TO INVESTIGATE EPIGENETIC CHANGES IN DAPHNIA MAGNA AFTER A 25-DAY CHRONIC EXTERNAL GAMMA IRRADIATION (GENERATION F0 EXPOSED TO 6.5 MUGY.H(-1) OR 41.3 MGY.H(-1)) AND THEIR POTENTIAL INHERITANCE BY SUBSEQUENT RECOVERING GENERATIONS, NAMELY, F2 (EXPOSED AS GERMLINE CELLS IN F1 EMBRYOS) AND F3 (THE FIRST TRULY UNEXPOSED GENERATION). EFFECTS ON SURVIVAL, GROWTH, AND REPRODUCTION WERE OBSERVED AND DNA WAS EXTRACTED FOR WHOLE-GENOME BISULFITE SEQUENCING IN ALL GENERATIONS. RESULTS SHOWED EFFECTS ON REPRODUCTION IN F0 BUT NO EFFECT IN THE SUBSEQUENT GENERATIONS F1, F2, AND F3. IN CONTRAST, WE OBSERVED SIGNIFICANT METHYLATION CHANGES AT SPECIFIC CPG POSITIONS IN EVERY GENERATION INDEPENDENT OF DOSE RATE, WITH A MAJORITY OF HYPOMETHYLATION. SOME OF THESE CHANGES WERE SHARED BETWEEN DOSE RATES AND BETWEEN GENERATIONS. ASSOCIATED GENE FUNCTIONS INCLUDED GENE FAMILIES AND GENES THAT WERE PREVIOUSLY SHOWN TO PLAY ROLES DURING EXPOSURE TO IONIZING RADIATION. COMMON METHYLATION CHANGES DETECTED BETWEEN GENERATIONS F2 AND F3 CLEARLY SHOWED THAT EPIGENETIC MODIFICATIONS CAN BE TRANSMITTED TO UNEXPOSED GENERATIONS, MOST LIKELY THROUGH THE GERMLINE, WITH POTENTIAL IMPLICATIONS FOR ENVIRONMENTAL RISK. 2018 3 2484 34 EPIGENETIC, TRANSCRIPTIONAL AND PHENOTYPIC RESPONSES IN TWO GENERATIONS OF DAPHNIA MAGNA EXPOSED TO THE DNA METHYLATION INHIBITOR 5-AZACYTIDINE. THE WATER FLEA DAPHNIA MAGNA IS A KEYSTONE SPECIES IN FRESHWATER ECOSYSTEMS AND HAS BEEN WIDELY USED AS A MODEL ORGANISM IN ENVIRONMENTAL ECOTOXICOLOGY. THIS AQUATIC CRUSTACEAN IS SENSITIVE TO ENVIRONMENTAL STRESSORS AND DISPLAYS CONSIDERABLE PLASTICITY IN ADAPTING TO CHANGING ENVIRONMENTAL CONDITIONS. PART OF THIS PLASTICITY MAY BE DUE TO EPIGENETIC REGULATION OF GENE EXPRESSION, INCLUDING CHANGES TO DNA METHYLATION AND HISTONE MODIFICATIONS. BECAUSE OF THE GENERALLY HYPOMETHYLATED GENOME OF THIS SPECIES, WE HYPOTHESIZED THAT THE HISTONE CODE MAY HAVE AN ESSENTIAL ROLE IN THE EPIGENETIC CONTROL AND THAT HISTONE MODIFICATIONS MIGHT BE AN EARLY MARKER FOR STRESS. THIS STUDY AIMS TO CHARACTERIZE THE EPIGENETIC, TRANSCRIPTIONAL AND PHENOTYPIC RESPONSES AND THEIR CAUSAL LINKAGES IN DIRECTLY EXPOSED ADULT (F0) DAPHNIA AND PERITONEAL EXPOSED NEONATES (F1) AFTER A CHRONIC (7-DAY) EXPOSURE TO A SUBLETHAL CONCENTRATION (10 MG/L) OF 5-AZACYTIDINE, A WELL-STUDIED VERTEBRATE DNA METHYLATION INHIBITOR. EXPOSURE OF THE F0 GENERATION SIGNIFICANTLY REDUCED THE CUMULATIVE FECUNDITY, ACCOMPANIED WITH DIFFERENTIAL EXPRESSION OF GENES IN THE ONE-CARBON-CYCLE METABOLIC PATHWAY. IN THE EPIGENOME OF THE F0 GENERATION, A DECREASE IN GLOBAL DNA METHYLATION, BUT NO SIGNIFICANT CHANGES ON H3K4ME3 OR H3K27ME3, WERE OBSERVED. IN THE F1 OFFSPRING GENERATION, CHANGES IN GENE EXPRESSION, A SIGNIFICANT REDUCTION IN GLOBAL DNA METHYLATION AND CHANGES IN HISTONE MODIFICATIONS WERE IDENTIFIED. THE RESULTS INDICATE THAT EXPOSURE DURING ADULTHOOD MAY RESULT IN MORE PRONOUNCED EFFECTS ON EARLY DEVELOPMENT IN THE OFFSPRING GENERATION, THOUGH INTERPRETATION OF THE DATA SHOULD BE CAREFULLY DONE SINCE BOTH THE EXPOSURE REGIME AND DEVELOPMENTAL PERIOD IS DIFFERENT IN THE TWO GENERATIONS EXAMINED. THE OBTAINED RESULTS IMPROVE OUR UNDERSTANDING OF CRUSTACEAN EPIGENETICS AND THE TOOLS DEVELOPED MAY PROMOTE USE OF EPIGENETIC MARKERS IN HAZARD ASSESSMENT OF ENVIRONMENTAL STRESSORS. 2019 4 2698 27 EXAMINING MULTI- AND TRANSGENERATIONAL BEHAVIORAL AND MOLECULAR ALTERATIONS RESULTING FROM PARENTAL EXPOSURE TO AN ENVIRONMENTAL PCB AND PBDE MIXTURE. POLYCHLORINATED BIPHENYLS (PCBS) AND POLYBROMINATED DIPHENYL ETHERS (PBDES) ARE PERSISTENT ORGANIC POLLUTANTS EXTENSIVELY USED DURING THE 20(TH) CENTURY AND STILL PRESENT IN AQUATIC ENVIRONMENTS DESPITE THEIR BAN. EFFECTS OF EXPOSURE TO THESE COMPOUNDS OVER GENERATIONS ARE POORLY DOCUMENTED. THEREFORE, OUR AIMS WERE TO CHARACTERIZE BEHAVIORAL RESPONSES AND UNDERLYING MOLECULAR MECHANISMS IN ZEBRAFISH EXPOSED TO AN ENVIRONMENTALLY RELEVANT MIXTURE OF PCBS AND PBDES AS WELL AS IN FOUR UNEXPOSED OFFSPRING GENERATIONS. ZEBRAFISH (F0) WERE CHRONICALLY EXPOSED FROM THE FIRST MEAL ONWARD TO A DIET SPIKED WITH A MIXTURE CONTAINING 22 PCB AND 7 PBDE CONGENERS IN PROPORTIONS AND CONCENTRATIONS REFLECTING ENVIRONMENTAL SITUATIONS (SIGMAPCBS = 1991 AND SIGMAPBDES = 411 NG/G). FOUR OFFSPRING GENERATIONS (F1 TO F4) WERE OBTAINED FROM THIS F0 AND WERE NOT FURTHER EXPOSED. BEHAVIOR WAS ASSESSED AT BOTH LARVAL AND ADULT STAGES. MECHANISMS RELATED TO BEHAVIORAL DEFECTS (HABENULA MATURATION AND C-FOS TRANSCRIPTION) AND METHYLATION (DNMTS TRANSCRIPTION) WERE MONITORED IN LARVAE. EXPOSED ADULT F0 AS WELL AS F1 AND F3 ADULTS DISPLAYED NO BEHAVIORAL CHANGE WHILE F2 EXPRESSED ANXIETY-LIKE BEHAVIOR. LARVAL BEHAVIOR WAS ALSO DISRUPTED, I.E. HYPERACTIVE AFTER LIGHT TO DARK TRANSITION IN F1 OR HYPOACTIVE IN F2, F3 AND F4. BEHAVIORAL DISRUPTIONS MAY BE RELATED TO DEFECT IN HABENULA MATURATION (OBSERVED IN F1) AND CHANGE IN C-FOS TRANSCRIPTION (OBSERVED IN F1 AND F2). TRANSCRIPTION OF THE GENE ENCODING DNA METHYLTRANSFERASE (DNMT3BA) WAS ALSO MODIFIED IN ALL GENERATIONS. OUR RESULTS LEAD US TO HYPOTHESIZE THAT CHRONIC DIETARY EXPOSURE TO AN ENVIRONMENTALLY RELEVANT MIXTURE OF PCB AND PBDE TRIGGERS MULTIGENERATIONAL AND TRANSGENERATIONAL MOLECULAR AND BEHAVIORAL DISRUPTIONS IN A VERTEBRATE MODEL. 2019 5 4923 23 PARENTAL DIURON EXPOSURE CAUSES LOWER HATCHABILITY AND ABNORMAL OVARIAN DEVELOPMENT IN OFFSPRING OF MEDAKA (ORYZIAS MELASTIGMA). DIURON IS ONE OF THE MOST WIDELY USED HERBICIDES WORLDWIDE. IT HAS BEEN WIDELY DETECTED IN VARIOUS AQUATIC ENVIRONMENTS, ESPECIALLY IN MARINE ECOSYSTEMS. ALTHOUGH DIRECT EFFECTS OF DIURON EXPOSURE ON VARIOUS ORGANISMS HAVE BEEN REPORTED, LITTLE IS KNOWN ABOUT ITS EFFECTS ON MARINE FISHES INCLUDING MULTIGENERATIONAL EFFECTS. HEREIN, THE FILIAL GENERATION (F1) OF DIURON-EXPOSED MARINE MEDAKA (ORYZIAS MELASTIGMA) (F0) WAS RAISED IN CLEAN SEAWATER FROM FERTILIZED EGGS TO ADULTHOOD AND USED AS A MARINE FISH MODEL TO STUDY THE POTENTIAL MULTIGENERATIONAL EFFECTS OF DIURON. WE FOUND THAT THE SUCCESSFUL HATCHING OF F1 LARVAE WAS SIGNIFICANTLY REDUCED AND THAT OVARIAN DEVELOPMENT IN F1 FEMALES WAS RETARDED. A SIGNIFICANT INCREASE IN THE PERCENTAGE OF PREVITELLOGENIC OOCYTES, ALONG WITH A VISUAL DECREASE IN THE PERCENTAGE OF VITELLOGENIC AND MATURE OOCYTES IN THE F1 OVARY, WERE OBSERVED. THE HORMONE LEVELS OF THE HYPOTHALAMUS-PITUITARY-GONAD-LIVER AXIS AND VITELLOGENIN-RELATED TRANSCRIPTION WERE DOWNREGULATED. IN ADDITION, THE MRNA LEVELS OF DNA METHYLTRANSFERASE IN THE BRAIN, OVARY AND LIVER OF F1 ADULT FISH EXHIBITED SIGNIFICANT UPREGULATION, SUGGESTING THAT THE PROBABLE UNDERLYING MULTIGENERATIONAL MECHANISM MIGHT BE ASSOCIATED WITH EPIGENETIC MODIFICATIONS. TAKEN TOGETHER, THESE RESULTS DEMONSTRATED THAT CHRONIC ENVIRONMENTAL DIURON EXPOSURE IN F0 MARINE MEDAKA CAN INHIBIT F1 OVARY DEVELOPMENT AND SUGGESTED THAT DIURON MAY AFFECT MARINE FISH THRIVING IN THE OCEAN. 2022 6 1816 25 EFFECTS OF CHRONIC EXPOSURE TO BENZOPHENONE AND DICLOFENAC ON DNA METHYLATION LEVELS AND REPRODUCTIVE SUCCESS IN A MARINE COPEPOD. THE UV-FILTER BENZOPHENONE AND THE ANTI-INFLAMMATORY DICLOFENAC ARE COMMONLY DETECTED IN THE ENVIRONMENT. THE AIM OF THIS STUDY WAS TO ASSESS THE MULTIGENERATIONAL EFFECTS OF CHRONIC EXPOSURE TO LOW CONCENTRATIONS OF THESE CHEMICALS ON TOXICITY AND DNA METHYLATION LEVELS IN THE COPEPOD GLADIOFERENS PECTINATUS. ACUTE TOXICITY TESTS WERE CONDUCTED TO DETERMINE THE SENSITIVITY OF G. PECTINATUS TO THE CHEMICALS. ALL CHEMICALS IMPACTED BREEDING, HATCHING AND EGG VIABILITY. DICLOFENAC (1 MG.L(-1)) REDUCED THE NUMBER OF EGGS PER GRAVID FEMALE. BENZOPHENONE (0.5 MG.L(-1)) DECREASED EGG HATCHING SUCCESS. EXPOSURE TO THE REFERENCE TOXICANT COPPER (0.02 MG.L(-1)) LED TO UNSUCCESSFUL HATCHING. EFFECTS ON DNA METHYLATION WAS ESTIMATED BY THE PERCENTAGE OF 5- METHYLCYTOSINE. THE TREATMENTS RESULTED IN STRONG DIFFERENCES IN DNA METHYLATION WITH INCREASED METHYLATION IN THE EXPOSED ANIMALS. THE TWO CHEMICALS IMPACTED BOTH EGG VIABILITY AND THE INDUCTION OF DIFFERENTIAL DNA METHYLATION, SUGGESTING POTENTIAL INTRA- AND TRANS-GENERATIONAL EVOLUTIONARY EFFECTS. 2018 7 3570 25 IMPACT OF JUVENILE HORMONE ANALOGUE INSECTICIDES ON THE WATER FLEA MOINA MACROCOPA: GROWTH, REPRODUCTION AND TRANSGENERATIONAL EFFECT. THE INCREASING QUANTITIES OF INSECTICIDES THAT LEACH INTO WATER BODIES SEVERELY AFFECT THE HEALTH OF THE AQUATIC ENVIRONMENT. JUVENILE HORMONE ANALOGUE (JHA) INSECTICIDES ARE ENDOCRINE DISRUPTERS THAT INTERFERE WITH HORMONAL ACTIVITY IN INSECTS BY MIMICKING JUVENILE HORMONES (JHS). BECAUSE THE STRUCTURE AND FUNCTIONS OF METHYL FARNESOATE IN CRUSTACEANS ARE SIMILAR TO THE INSECT JHS, EXOGENOUS JHA INSECTICIDES MAY CAUSE ADVERSE EFFECTS ON THE GROWTH AND REPRODUCTION IN CRUSTACEANS SIMILAR TO THOSE OBSERVED IN INSECTS. THIS STUDY EXAMINED THE TOXIC EFFECTS OF TWO JHA INSECTICIDES, METHOPRENE AND FENOXYCARB, ON THE WATER FLEA MOINA MACROCOPA. THE 24-H AND 48-H LC(50) VALUES FOR FENOXYCARB AND METHOPRENE WERE 0.53 AND 0.32 MG/L AND 0.70 AND 0.54 MG/L, RESPECTIVELY. CHRONIC EXPOSURE TO THE TWO JHAS CAUSED A SERIES OF TOXIC EFFECTS IN M. MACROCOPA, INCLUDING SHORTENING OF LIFE EXPECTANCY, REPRESSION OF BODY GROWTH, REDUCTION IN FECUNDITY, AND DISTURBED THE EXPRESSION OF GENES INVOLVED IN THE JH SIGNALING PATHWAY, IN CUTICLE DEVELOPMENT, AND IN THE CARBOHYDRATE, AMINO ACID, AND ATP METABOLIC PROCESSES. MOREOVER, JHA EXPOSURE IMPAIRED THE GROWTH AND REPRODUCTION OF THE OFFSPRING OF M. MACROCOPA EXPOSED TO JHAS, EVEN WHEN THE NEONATES WERE NOT EXPOSED TO THE CHEMICALS. IN ADDITION, CHANGES IN THE EXPRESSION OF GENES RELATED TO HISTONE METHYLATION INDICATE THAT EPIGENETIC CHANGES MAY PROMOTE TRANSGENERATIONAL IMPAIRMENT IN M. MACROCOPA. THESE RESULTS DEMONSTRATE THE TOXIC EFFECTS OF FENOXYCARB AND METHOPRENE ON NON-TARGET AQUATIC ORGANISMS. THE DAMAGES DONE BY THESE JHA INSECTICIDES TO THE AQUATIC ENVIRONMENT IS WORTHY OF OUR ATTENTION AND FURTHER STUDIES. 2020 8 3302 25 HIGH-FAT, SUCROSE AND SALT-RICH DIET DURING RAT SPERMATOGENESIS LEAD TO THE DEVELOPMENT OF CHRONIC KIDNEY DISEASE IN THE FEMALE OFFSPRING OF THE F2 GENERATION. EFFECTS OF FEEDING MALE RATS DURING SPERMATOGENESIS A HIGH-FAT, HIGH-SUCROSE AND HIGH-SALT DIET (HFSSD) OVER TWO GENERATIONS (F0 AND F1) ON RENAL OUTCOMES ARE UNKNOWN. MALE F0 AND F1 RATS WERE FED EITHER CONTROL DIET (F0CD+F1CD) OR HFSSD (F0HD+F1HD). THE OUTCOMES WERE GLOMERULAR FILTRATION RATE AND URINARY ALBUMIN EXCRETION IN F1 AND F2 OFFSPRING. IF BOTH OUTCOMES WERE ALTERED A MORPHOLOGICAL AND MOLECULAR ASSESSMENT WAS DONE. F2 OFFSPRING OF BOTH SEXES HAD A DECREASED GFR. HOWEVER, INCREASED URINARY ALBUMIN EXCRETION WAS ONLY OBSERVED IN FEMALE F2 F0HD+F1HD OFFSPRING COMPARED WITH CONTROLS. F0HD+F1HD FEMALE F2 OFFSPRING DEVELOPED GLOMERULOSCLEROSIS (+31%; P < .01) AND INCREASED RENAL INTERSTITIAL FIBROSIS (+52%; P < .05). RNA SEQUENCING FOLLOWED BY QRT-PCR VALIDATION SHOWED THAT FOUR GENES (ENPP6, TMEM144, CD300LF, AND ACTR3B) WERE DIFFERENTIALLY REGULATED IN THE KIDNEYS OF FEMALE F2 OFFSPRING. LNCRNA XR-146683.1 EXPRESSION DECREASED IN FEMALE F0HD+F1HD F2 OFFSPRING AND ITS EXPRESSION WAS (R = 0.44, P = .027) CORRELATED WITH THE EXPRESSION OF TMEM144. METHYLATION OF CPG ISLANDS IN THE PROMOTER REGION OF THE CD300LF GENE WAS INCREASED (P = .001) IN FEMALE F2 F0HD+F1HD OFFSPRING COMPARED TO CONTROLS. PROMOTER CPG ISLAND METHYLATION RATE OF CD300LF WAS INVERSELY CORRELATED WITH CD300LF MRNA EXPRESSION IN F2 FEMALE OFFSPRING (R = -0.483, P = .012). CD300LF MRNA EXPRESSION WAS INVERSELY CORRELATED WITH THE URINARY ALBUMIN-TO-CREATININE RATIO IN FEMALE F2 OFFSPRING (R = -0.588, P = .005). PATERNAL PRE-CONCEPTIONAL UNHEALTHY DIET GIVEN FOR TWO GENERATIONS PREDISPOSE FEMALE F2 OFFSPRING TO CHRONIC KIDNEY DISEASE DUE TO EPIGENETIC ALTERATIONS OF RENAL GENE EXPRESSION. PARTICULARLY, CD300LF GENE PROMOTOR METHYLATION WAS INVERSELY ASSOCIATED WITH CD300LF MRNA EXPRESSION AND CD300LF MRNA EXPRESSION ITSELF WAS INVERSELY ASSOCIATED WITH URINARY ALBUMIN EXCRETION IN F2 FEMALE OFFSPRING WHOSE FATHERS AND GRANDFATHERS GOT A PRE-CONCEPTIONAL UNHEALTHY DIET. 2022 9 4527 28 MULTIGENERATIONAL EFFECTS OF 4-METHYLBENZYLIDENE CAMPHOR (4-MBC) ON THE SURVIVAL, DEVELOPMENT AND REPRODUCTION OF THE MARINE COPEPOD TIGRIOPUS JAPONICUS. ONE OF THE MOST WIDELY USED ORGANIC UV FILTERS, 4-METHYLBENZYLIDENE CAMPHOR (4-MBC), IS PRESENT AT HIGH CONCENTRATIONS IN OFFSHORE WATERS. THE MARINE COPEPOD TIGRIOPUS JAPONICUS WAS EXPOSED TO DIFFERENT CONCENTRATIONS OF 4-MBC (I.E., 0, 0.5, 1, 5 AND 10MUGL(-1)) FOR 4 CONSECUTIVE GENERATIONS (F0-F3) TO EVALUATE THE IMPACT OF 4-MBC ON MARINE ECOSYSTEMS. THE RESULTS SHOWED THAT IN THE F0 GENERATION, 4-MBC CAUSED SIGNIFICANT LETHAL TOXICITY IN T. JAPONICAS AT CONCENTRATIONS OF 5 AND 10MUGL(-1) AND THE NAUPLII WERE MORE SENSITIVE TO 4-MBC TOXICITY THAN THE ADULTS. HOWEVER IN THE F1-F3 GENERATIONS, 4-MBC EXPOSURE DID NOT AFFECT THE SURVIVAL RATE. THE HATCHING RATE AND THE DEVELOPMENTAL DURATION FROM THE NAUPLII TO THE COPEPODITE (N-C) AND FROM THE NAUPLII TO ADULT (N-A) DECREASED SIGNIFICANTLY IN THE F1-F2 GENERATIONS AND IN THE F2-F3 GENERATIONS, RESPECTIVELY, EVEN AT THE LOWEST EXPOSURE CONCENTRATION (0.5MUGL(-1)). IN THE SUBSEQUENT TWO GENERATIONS (I.E., THE F4-F5 GENERATIONS) OF RECOVERY EXPOSURE IN CLEAN SEAWATER, THE GROWTH RATES OF THE ORIGINAL 4-MBC EXPOSURE GROUPS WERE STILL FASTER THAN THE CONTROL IN BOTH THE N-C AND N-A STAGES, SUGGESTING POSSIBLE TRANSGENERATIONAL GENETIC AND/OR EPIGENETIC CHANGES UPON CHRONIC 4-MBC EXPOSURE. THE EXPRESSION OF THE ECDYSONE RECEPTOR GENE WAS UP-REGULATED BY 4-MBC, WHICH WAS CONSISTENT WITH THE DECREASE OF THE N-C/N-A DURATION. IN ADDITION, 4-MBC MAY INDUCE OXIDATIVE STRESS AND TRIGGER APOPTOSIS IN T. JAPONICAS, RESULTING IN DEVELOPMENTAL, REPRODUCTIVE AND EVEN LETHAL TOXICITY. A PRELIMINARY RISK ASSESSMENT SUGGESTED THAT UNDER ENVIRONMENTALLY REALISTIC CONCENTRATIONS, 4-MBC HAD SIGNIFICANT POTENTIAL TO POSE A THREAT TO MARINE CRUSTACEANS AND MARINE ECOSYSTEMS. 2018 10 3109 30 GENOTOXIC AND EPIGENETIC EFFECTS OF DIURON IN THE PACIFIC OYSTER: IN VITRO EVIDENCE OF INTERACTION BETWEEN DNA DAMAGE AND DNA METHYLATION. RECENTLY, RESEARCH HAS CONTRIBUTED TO BETTER KNOWLEDGE ON THE OCCURRENCE OF PESTICIDES IN COASTAL WATER BY IDENTIFYING FREQUENTLY DETECTED SUBSTANCES, THEIR CONCENTRATION RANGE AND THEIR ACUTE AND CHRONIC TOXICITY FOR ORGANISMS. PESTICIDE POLLUTION IS OF PARTICULAR CONCERN IN FRANCE DUE TO IMPORTANT AGRICULTURAL ACTIVITIES AND PRESENCE OF SEVERAL EXOREIC CATCHMENT AREAS THAT VEHICLE PESTICIDES UP TO COASTAL WATERS, IMPACTING NON-TARGET MARINE SPECIES. SEVERAL ECOTOXICOLOGY QUESTIONS REMAIN TO BE ADDRESSED CONCERNING THE LONG-TERM EFFECTS OF CHRONIC PESTICIDE EXPOSURE AND THE MECHANISMS INVOLVED IN ADAPTATION TO CHEMICAL STRESS. IN THE PRESENT STUDY, WE BROUGHT NEW INSIGHTS ON THE GENETIC AND EPIGENETIC EFFECTS OF THE HERBICIDE DIURON IN OYSTER GENITORS. DURING GAMETOGENESIS, WE EXPOSED CRASSOSTREA GIGAS TO ENVIRONMENTALLY REALISTIC HERBICIDE CONCENTRATIONS (0.2-0.3 MUG L(-1) DURING TWO 7-DAY PERIODS AT HALF-COURSE AND END OF GAMETOGENESIS). DIURON EXPOSURE WAS SHOWN TO DECREASE GLOBAL DNA METHYLATION AND TOTAL METHYLTRANSFERASE ACTIVITY IN WHOLE OYSTER TISSUE; THIS IS CONSISTENT WITH THE PREVIOUS OBSERVATION OF A SIGNIFICANT DECREASE IN DNMT1 GENE EXPRESSION. DIURON EFFECT SEEMED TO BE TISSUE-SPECIFIC; HYPERMETHYLATION WAS DETECTED IN THE DIGESTIVE GLAND, WHEREAS DIURON EXPOSURE HAD NO EFFECT ON GILL AND GONAD TISSUE. THE GENOTOXICITY OF DIURON WAS CONFIRMED BY THE DETECTION OF ONE ADDUCT IN GONAD DNA. BY USING IN VITRO APPROACHES AND HUMAN DNMT1 (DNMT1 HAS NOT BEEN PURIFIED YET IN BIVALVES), THE PRESENCE OF DNA LESIONS (ADDUCT, 8-OXODGUO) WAS SHOWN TO INTERFERE WITH DNMT1 ACTIVITY, INDICATING A COMPLEX INTERACTION BETWEEN DNA DAMAGE AND DNA METHYLATION. BASED ON OUR RESULTS, WE PROPOSE MECHANISMS TO EXPLAIN THE EFFECT OF DIURON EXPOSURE ON DNA METHYLATION, A WIDESPREAD EPIGENETIC MARK. 2021 11 1768 26 EARLY-LIFE LEAD EXPOSURE RESULTS IN DOSE- AND SEX-SPECIFIC EFFECTS ON WEIGHT AND EPIGENETIC GENE REGULATION IN WEANLING MICE. AIMS: EPIDEMIOLOGICAL AND ANIMAL DATA SUGGEST THAT THE DEVELOPMENT OF ADULT CHRONIC CONDITIONS IS INFLUENCED BY EARLY-LIFE EXPOSURE-INDUCED CHANGES TO THE EPIGENOME. THIS STUDY INVESTIGATES THE EFFECTS OF PERINATAL LEAD (PB) EXPOSURE ON DNA METHYLATION AND BODYWEIGHT IN WEANLING MICE. MATERIALS & METHODS: VIABLE YELLOW AGOUTI (A(VY)) MOUSE DAMS WERE EXPOSED TO 0, 2.1, 16 AND 32 PPM PB ACETATE BEFORE CONCEPTION THROUGH WEANING. EPIGENETIC EFFECTS WERE EVALUATED BY SCORING COAT COLOR OF A(VY)/A OFFSPRING AND QUANTITATIVE BISULFITE SEQUENCING OF TWO RETROTRANSPOSON-DRIVEN (A(VY) AND CDK5 ACTIVATOR-BINDING PROTEIN INTRACISTERNAL A PARTICLE ELEMENT) AND TWO IMPRINTED (IGF2 AND IGF2R) LOCI IN TAIL DNA. RESULTS: MATERNAL BLOOD PB LEVELS WERE BELOW THE LIMIT OF DETECTION IN CONTROLS, AND 4.1, 25.1 AND 32.1 MICROG/DL FOR EACH DOSE, RESPECTIVELY. PB EXPOSURE WAS ASSOCIATED WITH A TREND OF INCREASED WEAN BODYWEIGHT IN MALES (P = 0.03) AND ALTERED COAT COLOR IN A(VY)/A OFFSPRING. DNA METHYLATION AT A(VY) AND THE CDK5 ACTIVATOR-BINDING PROTEIN INTRACISTERNAL A-PARTICLE ELEMENT WAS SIGNIFICANTLY DIFFERENT FROM CONTROLS FOLLOWING A CUBIC TREND (P = 0.04; P = 0.01), WITH MALE-SPECIFIC EFFECTS AT THE A(VY) LOCUS. IMPRINTED GENES DID NOT SHIFT IN METHYLATION ACROSS EXPOSURES. CONCLUSION: DOSE- AND SEX-SPECIFIC RESPONSES IN BODYWEIGHT AND DNA METHYLATION INDICATE THAT PB ACTS ON THE EPIGENOME IN A LOCUS-SPECIFIC FASHION, DEPENDENT ON THE GENOMIC FEATURE HOSTING THE CPG SITE OF INTEREST, AND THAT SEX IS A FACTOR IN EPIGENETIC RESPONSE. 2013 12 6777 18 [ASSOCIATION OF P-MOBILE ELEMENT ACTIVITY AND DNA METHYLATION PATTERN CHANGES IN THE CONDITIONS OF DROSOPHILA MELANOGASTER PROLONGED IRRADIATION]. ASSOCIATION OF THE RADIOSENSITIVITY AND EPIGENETIC PATTERN DNA CHANGES AT THE CONDITIONS OF PROLONGED IRRADIATION WAS INVESTIGATED. TWO LABORATORY DROSOPHILA MELANOGASTER STRAINS (CANTON-S AND RI) IRRADIATED FOR 20 GENERATIONS TO LOW DOSES RATE (1.2 X 10(-1), 0.8 X 10(-8) AND 0.12 X 10(-8) GY/S) WERE USED AS EXPERIMENTAL OBJECTS. DNA FOR THE ANALYSIS WAS EXTRACTED SEPARATELY FOR THE FLIES OF MALES AND FEMALES. RESTRICTION ENDONUCLEASES GLUL, GLAL WERE USED. RESTRICTION ANALYSIS HAS SHOWN THAT THERE ARE DIFFERENT DNA METHYLATED PATTERNS FOR MALES AND FEMALES AS FOR CONTROL AND EXPOSED VARIANTS. AT THE CHRONIC IRRADIATION THERE WAS THE DECLINE OF METHYLATION LEVEL AT THE ENZYMES GLUL, GLAL SITES RECOGNITION. 2010 13 4924 25 PARENTAL HYPOXIC EXPOSURE CONFERS OFFSPRING HYPOXIA RESISTANCE IN ZEBRAFISH (DANIO RERIO). PARENTAL INFLUENCES ARE A POTENTIALLY IMPORTANT COMPONENT OF TRANSGENERATIONAL TRANSFER OF PHENOTYPE IN VERTEBRATES. THIS STUDY EXAMINED HOW CHRONIC HYPOXIC EXPOSURE ON ADULT ZEBRAFISH (DANIO RERIO) AFFECTED THE PHENOTYPE OF THEIR OFFSPRING. SEPARATE ADULT POPULATIONS WERE EXPOSED TO HYPOXIA (13.1 KPA O(2)) OR NORMOXIA (21.1 KPA O(2)) FOR PERIODS RANGING FROM 1 TO 12 WEEKS. ADULTS WERE THEN RETURNED TO NORMOXIA AND BRED WITHIN EXPERIMENTAL GROUPS. ADULT FECUNDITY AND EGG CHARACTERISTICS (VOLUME OF EGG, YOLK AND PERIVITELLINE FLUID) WERE ASSESSED. SUBSEQUENTLY, LARVAL BODY LENGTH, TIME TO LOSS OF EQUILIBRIUM IN SEVERE HYPOXIA (~4 KPA O(2)), AND CRITICAL THERMAL MINIMA (CT(MIN)) AND MAXIMA (CT(MAX)) WERE MEASURED AT 6, 9, 12, 15, 18, 21 AND 60 DAYS POST-FERTILIZATION (D.P.F.). ADULT FECUNDITY WAS DEPRESSED BY HYPOXIC EXPOSURE. EGG COMPONENT VOLUMES WERE ALSO DEPRESSED IN ADULTS EXPOSED TO 1-2 WEEKS OF HYPOXIA, BUT RETURNED TO CONTROL LEVELS FOLLOWING LONGER HYPOXIC EXPOSURE. ADULT HYPOXIC EXPOSURES OF >1 WEEK RESULTED IN LONGER BODY LENGTHS IN THEIR LARVAL OFFSPRING. TIME TO LOSS OF EQUILIBRIUM IN SEVERE HYPOXIA (I.E. HYPOXIC RESISTANCE) IN CONTROL LARVAE DECREASED FROM 6 TO 12 D.P.F., REMAINING CONSTANT THEREAFTER. NOTABLY, HYPOXIC RESISTANCE FROM 6 TO 18 D.P.F. WAS ~15% LOWER IN LARVAE WHOSE PARENTS WERE EXPOSED TO JUST 1 WEEK OF CHRONIC HYPOXIA, BUT RESISTANCE WAS SIGNIFICANTLY INCREASED BY ~24-30% IN 6-18 D.P.F. LARVAE FROM ADULTS EXPOSED TO 2, 3 OR 4 WEEKS OF HYPOXIA. CT(MIN) (~10-12 DEGREES C) AND CT(MAX) (~39.5 DEGREES C) WERE UNCHANGED BY PARENTAL HYPOXIC EXPOSURE. THIS STUDY DEMONSTRATES THAT PARENTAL HYPOXIC EXPOSURE IN ADULT ZEBRAFISH HAS PROFOUND EPIGENETIC EFFECTS ON THE MORPHOLOGICAL AND PHYSIOLOGICAL PHENOTYPE OF THEIR OFFSPRING. 2012 14 184 28 ACCOUNTING FOR TRANSGENERATIONAL EFFECTS OF TOXICANT EXPOSURE IN POPULATION MODELS ALTERS THE PREDICTED LONG-TERM POPULATION STATUS. ACUTE ENVIRONMENTAL STRESSORS SUCH AS SHORT-TERM EXPOSURE TO POLLUTANTS CAN HAVE LASTING EFFECTS ON ORGANISMS, POTENTIALLY IMPACTING FUTURE GENERATIONS. PARENTAL EXPOSURE TO TOXICANTS CAN RESULT IN CHANGES TO THE EPIGENOME (E.G., DNA METHYLATION) THAT ARE PASSED DOWN TO SUBSEQUENT, UNEXPOSED GENERATIONS. HOWEVER, IT IS DIFFICULT TO GAUGE THE CUMULATIVE POPULATION-SCALE IMPACTS OF EPIGENETIC EFFECTS FROM LABORATORY EXPERIMENTS ALONE. HERE, WE DEVELOPED A SIZE- AND AGE-STRUCTURED DELAY-COORDINATE POPULATION MODEL TO EVALUATE THE LONG-TERM CONSEQUENCES OF EPIGENETIC MODIFICATIONS ON POPULATION SUSTAINABILITY. THE MODEL EMULATED CHANGES IN GROWTH, MORTALITY, AND FECUNDITY IN THE F0, F1, AND F2 GENERATIONS OBSERVED IN EXPERIMENTS IN WHICH LARVAL MENIDIA BERYLLINA WERE EXPOSED TO ENVIRONMENTALLY RELEVANT CONCENTRATIONS OF BIFENTHRIN (BIF), ETHINYLESTRADIOL (EE2), LEVONORGESTREL (LV), OR TRENBOLONE (TB) IN THE PARENT GENERATION (F0) AND REARED IN CLEAN WATER UP TO THE F2 GENERATION. OUR ANALYSIS SUGGESTS POTENTIALLY DRAMATIC POPULATION-LEVEL EFFECTS OF REPEATED, CHRONIC EXPOSURES OF EARLY-LIFE STAGE FISH THAT ARE NOT CAPTURED BY MODELS NOT ACCOUNTING FOR THOSE EFFECTS. SIMULATED EXPOSURES LED TO SUBSTANTIAL DECLINES IN POPULATION ABUNDANCE (LV AND BIF) OR NEAR-EXTINCTION (EE2 AND TB) WITH THE EXACT TRAJECTORY AND TIMELINE OF POPULATION DECLINE DEPENDENT ON THE COMBINATION OF F0, F1, AND F2 EFFECTS PRODUCED BY EACH COMPOUND. EVEN ACUTE ONE-TIME EXPOSURES OF EACH COMPOUND LED TO DECLINES AND RECOVERY OVER MULTIPLE YEARS DUE TO LAGGED EPIGENETIC EFFECTS. THESE RESULTS DEMONSTRATE THE POTENTIAL FOR ENVIRONMENTALLY RELEVANT CONCENTRATIONS OF COMMONLY USED COMPOUNDS TO IMPACT THE POPULATION DYNAMICS AND SUSTAINABILITY OF AN ECOLOGICALLY RELEVANT SPECIES AND MODEL ORGANISM. 2022 15 73 30 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 16 985 17 CHRONIC RADIATION EXPOSURE AS AN ECOLOGICAL FACTOR: HYPERMETHYLATION AND GENETIC DIFFERENTIATION IN IRRADIATED SCOTS PINE POPULATIONS. GENETIC AND EPIGENETIC CHANGES WERE INVESTIGATED IN CHRONICALLY IRRADIATED SCOTS PINE (PINUS SYLVESTRIS L.) POPULATIONS FROM TERRITORIES THAT WERE HEAVILY CONTAMINATED BY RADIONUCLIDES AS RESULT OF THE CHERNOBYL NUCLEAR POWER PLANT ACCIDENT. IN COMPARISON TO THE REFERENCE SITE, THE GENETIC DIVERSITY REVEALED BY ELECTROPHORETIC MOBILITY OF AFLPS WAS FOUND TO BE SIGNIFICANTLY HIGHER AT THE RADIOACTIVELY CONTAMINATED AREAS. IN ADDITION, THE GENOME OF PINE TREES WAS SIGNIFICANTLY HYPERMETHYLATED AT 4 OF THE 7 AFFECTED SITES. 2018 17 6526 22 TRANSCRIPTIONAL CHANGES IN THE OVARIES OF PERCH FROM CHERNOBYL. FISH HAVE BEEN HIGHLY EXPOSED TO RADIATION IN FRESHWATER SYSTEMS AFTER THE CHERNOBYL NUCLEAR POWER PLANT (NPP) ACCIDENT IN 1986 AND IN FRESHWATER AND MARINE SYSTEMS AFTER THE MORE RECENT FUKUSHIMA NPP ACCIDENT IN 2011. IN THE YEARS AFTER THE ACCIDENT, THE RADIOACTIVITY LEVELS RAPIDLY DECLINED DUE TO RADIOACTIVE DECAY AND ENVIRONMENTAL PROCESSES, BUT CHRONIC LOWER DOSE EXPOSURES PERSISTED. TO GAIN INSIGHTS INTO THE LONG-TERM EFFECTS OF ENVIRONMENTAL LOW DOSE RADIATION ON FISH OVARIES DEVELOPMENT, A HIGH-THROUGHPUT TRANSCRIPTOMIC APPROACH INCLUDING A DE NOVO ASSEMBLY WAS APPLIED TO DIFFERENT GONAD PHENOTYPES OF FEMALE PERCH: DEVELOPED GONADS FROM REFERENCE LAKES, DEVELOPED/IRRADIATED FROM MEDIUM CONTAMINATED LAKE, AND BOTH DEVELOPED/IRRADIATED AND UNDEVELOPED FROM MORE HIGHLY CONTAMINATED LAKES. THIS IS THE MOST COMPREHENSIVE ANALYSIS TO DATE OF THE GENE RESPONSES IN WILDLIFE REPRODUCTIVE SYSTEM TO RADIATION. SOME GENE RESPONSES THAT WERE MODULATED IN IRRADIATED GONADS WERE FOUND TO BE INVOLVED IN BIOLOGICAL PROCESSES INCLUDING CELL DIFFERENTIATION AND PROLIFERATION (GGNB2, MOD5, RERGL), CYTOSKELETON ORGANIZATION (K1C18, MTPN), GONAD DEVELOPMENT (NELL2, TCP4), LIPID METABOLISM (LDAH, AT11B, NLTP), REPRODUCTION (CYB5, CYP17A, OVOS), DNA DAMAGE REPAIR (WDHD1, RAD51, HUS1), AND EPIGENETIC MECHANISMS (DMAP1). IDENTIFICATION OF THESE GENES PROVIDES A BETTER UNDERSTANDING OF THE UNDERLYING MOLECULAR MECHANISMS UNDERPINNING THE DEVELOPMENT OF THE GONAD PHENOTYPES OF WILD PERCH AND HOW FISH MAY RESPOND TO CHRONIC EXPOSURE TO RADIATION IN THEIR NATURAL ENVIRONMENT, THOUGH CAUSAL ATTRIBUTION OF GENE RESPONSES REMAINS UNCLEAR IN THE UNDEVELOPED GONADS. 2020 18 4077 19 MATERNAL INFLAMMATION INDUCES SPATIAL LEARNING AND MEMORY IMPAIRMENT IN THE F1 AND F2 GENERATIONS OF MICE VIA SEX-SPECIFIC EPIGENETIC MECHANISMS. MOUNTING EVIDENCE INDICATES THAT HISTONE MODIFICATIONS ARE INVOLVED IN AGING-ASSOCIATED COGNITIVE DECLINE (AACD) AND CAN BE TRANSMITTED TO OFFSPRING OVER MULTIPLE GENERATIONS UNDER CONDITIONS OF STRESS. HERE, WE INVESTIGATED THE EFFECTS OF MATERNAL SUB-CHRONIC INFLAMMATION CAUSED BY LIPOPOLYSACCHARIDE (LPS) ON AACD AND HISTONE MODIFICATIONS IN THE F1 AND F2 GENERATIONS OF EXPERIMENTAL MICE AS WELL AS THE POTENTIAL SEX SPECIFICITY OF INTERGENERATIONAL EFFECTS. IN BRIEF, F0-GENERATION CD-1 DAMS WERE EXPOSED TO LPS (50 MICROG/KG) OR SALINE (CON) DURING LATE PREGNANCY. SUBSEQUENTLY, F1 MALES AND FEMALES (AT 2 MONTHS-OF-AGE) FROM THE LPS TREATMENT GROUP WERE MATED WITH NON-LITTERMATES FROM THE LPS GROUP OR WILD-TYPE MICE TO PRODUCE F2 GENERATIONS OF PARENTAL- (F2-LPS(2)), PATERNAL- (F2M-LPS(1)) AND MATERNAL-ORIGIN (F2F-LPS(1)) MICE. THEN, CON-F1 MALES AND FEMALES WERE MATED WITH WILD-TYPE MICE TO GENERATE F2 GENERATIONS OF PATERNAL- (F2M-CON(1)) AND MATERNAL-ORIGIN (F2F-CON(1)). NEXT, WE EVALUATED THE COGNITIVE ABILITY AND LEVELS OF HIPPOCAMPAL H4K12AC AND H3K9ME3 IN THE F1 AND F2 OFFSPRING AT 3- AND 13 MONTHS-OF-AGE. OVERALL, F1 MALE AND FEMALE LPS GROUPS PRESENTED WITH ELEVATED CORTICOSTERONE (P < 0.001, P = 0.036, P = 0.025, 0.012, RESPECTIVELY) AND CYTOKINE RESPONSES, POORER COGNITIVE PERFORMANCE (ALL P < 0.05) AND H3K9 HYPERMETHYLATION AND H4K12 HYPOACETYLATION IN THE DORSAL HIPPOCAMPUS (ALL P < 0.05); THESE ISSUES WERE CARRIED OVER TO THE F2 GENERATION VIA THE PARENTS, PREDOMINANTLY IN THE PATERNAL LINEAGE. MOREOVER, THE LEVELS OF H3K9ME3 AND H4K12AC WERE SIGNIFICANT CORRELATED WITH COGNITIVE PERFORMANCE (ALL P < 0.05), REGARDLESS OF WHETHER INFLAMMATORY INSULTS HAD BEEN INCURRED DIRECTLY OR INDIRECTLY. THESE FINDINGS INDICATED THAT GESTATIONAL INFLAMMATORY INSULTS IN THE F0 GENERATION ACCELERATED AACD IN THE F2 GENERATION, ALONG WITH H3K9 HYPERMETHYLATION AND H4K12 HYPOACETYLATION IN THE HIPPOCAMPUS, AND THAT THESE ISSUES WERE DERIVED FROM THE F1 PARENTS, ESPECIALLY FROM THE F1 FATHERS. 2022 19 6555 28 TRANSGENERATIONAL EFFECTS OF GAMMA RADIATION DOSE AND DOSE RATE ON DROSOPHILA FLIES IRRADIATED AT AN EARLY EMBRYONAL STAGE. IONIZING RADIATION (IR) KILLS CELLS MAINLY THROUGH INDUCTION OF DNA DAMAGES AND THE SURVIVING CELLS MAY SUFFER FROM MUTATIONS. TRANSGENERATIONAL EFFECTS OF IR ARE WELL DOCUMENTED, BUT THE EXACT MECHANISMS UNDERLYING THEM ARE LESS WELL UNDERSTOOD; THEY INCLUDE INDUCTION OF MUTATIONS IN GERM CELLS AND EPIGENETIC INHERITANCE. PREVIOUSLY, EFFECTS IN THE OFFSPRING OF MICE AND ZEBRAFISH EXPOSED TO IR HAVE BEEN REPORTED. A FEW STUDIES ALSO SHOWED INDICATIONS OF TRANSGENERATIONAL EFFECTS OF RADIATION IN HUMANS, PARTICULARLY IN NUCLEAR POWER WORKERS. IN THE PRESENT PROJECT, SHORT- AND LONG-TERM EFFECTS OF LOW-DOSE-RATE (LDR; 50 AND 97 MGY/H) AND HIGH-DOSE-RATE (HDR; 23.4, 47.1 AND 495 GY/H) IR IN DROSOPHILA EMBRYOS WERE INVESTIGATED. THE EMBRYOS WERE IRRADIATED AT DIFFERENT DOSES AND DOSE RATES AND RADIOSENSITIVITY AT DIFFERENT DEVELOPMENTAL STAGES WAS INVESTIGATED. ALSO, THE SURVIVAL OF LARVAE, PUPAE AND ADULTS DEVELOPED FROM EMBRYOS IRRADIATED AT AN EARLY STAGE (30 MIN AFTER EGG LAYING) WERE STUDIED. THE LARVAL CRAWLING AND PUPATION HEIGHT ASSAYS WERE APPLIED TO INVESTIGATE RADIATION EFFECTS ON LARVAL LOCOMOTION AND PUPATION BEHAVIOR, RESPECTIVELY. IN PARALLEL, THE OFFSPRING FROM 3 GY IRRADIATED EARLY-STAGE EMBRYOS WERE FOLLOWED UP TO 12 GENERATIONS AND ABNORMAL PHENOTYPES WERE STUDIED. ACUTE EXPOSURE OF EMBRYOS AT DIFFERENT STAGES OF DEVELOPMENT SHOWED THAT THE EARLY STAGE EMBRYO IS THE MOST SENSITIVE. THE EFFECTS ON LARVAL LOCOMOTION SHOWED NO SIGNIFICANT DIFFERENCES BETWEEN THE DOSE RATES BUT A SIGNIFICANT DECREASE OF LOCOMOTION ACTIVITY ABOVE 7 GY WAS OBSERVED. THE RESULTS INDICATE THAT EMBRYOS EXPOSED TO THE LOW DOSE RATES HAVE SHORTER ECLOSION TIMES. AT THE SAME CUMULATIVE DOSE (1 UP TO 7 GY), HDR IS MORE EMBRYOTOXIC THAN LDR. WE ALSO FOUND A RADIATION-INDUCED DEPIGMENTATION ON MALES (A5 SEGMENT OF THE DORSAL ABDOMEN, A5PIG(-)) THAT CAN BE TRANSMITTED UP TO 12 GENERATIONS. THE PHENOMENON DOES NOT FOLLOW THE CLASSICAL MENDELIAN LAWS OF SEGREGATION. 2022 20 3300 22 HIGH-FAT DIET REPROGRAMS THE EPIGENOME OF RAT SPERMATOZOA AND TRANSGENERATIONALLY AFFECTS METABOLISM OF THE OFFSPRING. OBJECTIVES: CHRONIC AND HIGH CONSUMPTION OF FAT CONSTITUTES AN ENVIRONMENTAL STRESS THAT LEADS TO METABOLIC DISEASES. WE HYPOTHESIZED THAT HIGH-FAT DIET (HFD) TRANSGENERATIONALLY REMODELS THE EPIGENOME OF SPERMATOZOA AND METABOLISM OF THE OFFSPRING. METHODS: F0-MALE RATS FED EITHER HFD OR CHOW DIET FOR 12 WEEKS WERE MATED WITH CHOW-FED DAMS TO GENERATE F1 AND F2 OFFSPRING. MOTILE SPERMATOZOA WERE ISOLATED FROM F0 AND F1 BREEDERS TO DETERMINE DNA METHYLATION AND SMALL NON-CODING RNA (SNCRNA) EXPRESSION PATTERN BY DEEP SEQUENCING. RESULTS: NEWBORN OFFSPRING OF HFD-FED FATHERS HAD REDUCED BODY WEIGHT AND PANCREATIC BETA-CELL MASS. ADULT FEMALE, BUT NOT MALE, OFFSPRING OF HFD-FED FATHERS WERE GLUCOSE INTOLERANT AND RESISTANT TO HFD-INDUCED WEIGHT GAIN. THIS PHENOTYPE WAS PERPETUATED IN THE F2 PROGENY, INDICATING TRANSGENERATIONAL EPIGENETIC INHERITANCE. THE EPIGENOME OF SPERMATOZOA FROM HFD-FED F0 AND THEIR F1 MALE OFFSPRING SHOWED COMMON DNA METHYLATION AND SMALL NON-CODING RNA EXPRESSION SIGNATURES. ALTERED EXPRESSION OF SPERM MIRNA LET-7C WAS PASSED DOWN TO METABOLIC TISSUES OF THE OFFSPRING, INDUCING A TRANSCRIPTOMIC SHIFT OF THE LET-7C PREDICTED TARGETS. CONCLUSION: OUR RESULTS PROVIDE INSIGHT INTO MECHANISMS BY WHICH HFD TRANSGENERATIONALLY REPROGRAMS THE EPIGENOME OF SPERM CELLS, THEREBY AFFECTING METABOLIC TISSUES OF OFFSPRING THROUGHOUT TWO GENERATIONS. 2016