1 830 132 CHARACTERIZATION OF STRESS RESPONSE INVOLVED IN CHICKEN MYOPATHY. MYOPATHIES (WOODY BREAST (WB) AND WHITE STRIPING (WS)) OF BROILER CHICKENS HAVE BEEN CORRELATED WITH FAST GROWTH. RECENT STUDIES REPORTED THAT LOCALIZED HYPOXIA AND METABOLIC IMPAIRMENT MAY INVOLVE IN THESE MYOPATHIES OF BIRDS. IN ORDER TO BETTER UNDERSTAND THE STRESS RESPONSE MECHANISMS AFFECTING MYOPATHIES OF BROILERS, THE AIM OF THIS STUDY WAS TO EXAMINE EFFECTS OF WB AND BOTH WB/WS ON STRESS HORMONE CORTICOSTERONE (CORT) LEVELS AND EXPRESSIONAL CHANGES OF STRESS RESPONSE GENES INCLUDING GLUCOCORTICOID (GC) RECEPTOR (GR), 11BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11BETA-HSD1), DNA METHYLATION REGULATORS (DNMTS), AND ARGININE VASOTOCIN RECEPTOR 1A AND 1B (V1AR, V1BR). RESULTS OF RADIOIMMUNOASSAY SHOWED THAT CORT LEVELS OF WB AND WB/WS BIRDS WERE SIGNIFICANTLY HIGHER COMPARED TO CON (P < 0.05), HOWEVER, THE COMBINATION OF WB/WS WAS NOT SIGNIFICANTLY HIGHER THAN WB BIRDS, IMPLYING THAT THE EFFECTS OF WB AND WS ON CORT ARE NOT SYNERGISTIC. HEPATIC GR EXPRESSION OF BOTH WB AND WB/WS BIRDS WERE SIGNIFICANTLY HIGHER COMPARED TO CON (P < 0.05). HOWEVER, GR EXPRESSION LEVELS IN BREAST MUSCLE OF BOTH WB AND WB/WS BIRDS WERE DECREASED COMPARED TO CON (P < 0.05). HEPATIC 11BETA-HSD1 EXPRESSION WAS INCREASED ONLY IN WB/WS BIRDS COMPARED TO CON BIRDS WITH NO SIGNIFICANT DIFFERENCE BETWEEN CON AND WB BIRDS. 11BETA-HSD1 EXPRESSION WAS DECREASED AND INCREASED IN WB AND WB/WS BIRDS COMPARED TO CON, RESPECTIVELY, IN BREAST MUSCLE (P < 0.05). DNMT1 EXPRESSION WAS SIGNIFICANTLY DECREASED IN BOTH MUSCLE AND LIVER OF WB BIRDS, AND IN MUSCLE OF WB/WS BIRDS, BUT NOT IN LIVER OF WB/WS BIRDS, INDICATING DIFFERENTIAL EFFECTS OF WS ON THE EPIGENETICAL STRESS RESPONSE OF MUSCLE AND LIVER COMPARED TO WB. V1AR EXPRESSION WAS SIGNIFICANTLY INCREASED IN MUSCLE OF WB BIRDS, AND IN LIVER OF WB/WS BIRDS COMPARED TO CON BIRDS (P < 0.05). V1BR WAS NOT CHANGED IN MUSCLE AND LIVER OF WB BIRDS COMPARED TO CON BIRDS. TAKEN TOGETHER, RESULTS SUGGEST THAT GC-INDUCED MYOPATHIES OCCUR IN FAST-GROWING BROILER CHICKENS AND CIRCULATING CORT LEVEL MIGHT BE A SIGNIFICANT BIOCHEMICAL MARKER OF MYOPATHIES (WB AND WS) OF BIRDS. IN ADDITION, CHRONIC STRESS RESPONSES IN BREAST MUSCLE AND TISSUE-SPECIFIC EPIGENETIC CHANGES OF STRESS RESPONSE GENES BY DNMTS MAY PLAY A CRITICAL ROLE IN THE OCCURRENCE OF MYOPATHIES. 2020 2 4934 32 PATERNAL CHRONIC FOLATE SUPPLEMENTATION INDUCED THE TRANSGENERATIONAL INHERITANCE OF ACQUIRED DEVELOPMENTAL AND METABOLIC CHANGES IN CHICKENS. INCREASING EVIDENCE INDICATES THAT PATERNAL DIET CAN RESULT IN METABOLIC CHANGES IN OFFSPRING, BUT THE DEFINITE MECHANISM REMAINS UNCLEAR IN BIRDS. HERE, WE FED BREEDER COCKS FIVE DIFFERENT DIETS CONTAINING 0, 0.25, 1.25, 2.50 AND 5.00 MG KG(-1) FOLATE THROUGHOUT LIFE. PATERNAL FOLATE SUPPLEMENTATION (FS) WAS BENEFICIAL TO THE GROWTH AND ORGAN DEVELOPMENT OF BROILER OFFSPRING. MOST IMPORTANTLY, THE LIPID AND GLUCOSE METABOLISM OF BREEDER COCKS AND BROILER OFFSPRING WERE AFFECTED BY PATERNAL FS, ACCORDING TO BIOCHEMICAL AND METABOLOMIC ANALYSES. WE FURTHER EMPLOYED GLOBAL ANALYSES OF HEPATIC AND SPERMATOZOAL MESSENGER RNA (MRNA), LONG NON-CODING RNA (LNCRNA) AND MICRO RNA (MIRNA). SOME KEY GENES INVOLVED IN THE GLYCOLYSIS OR GLUCONEOGENESIS PATHWAY AND THE PPAR SIGNALLING PATHWAY, INCLUDING PEPCK, ANGPTL4 AND THRSP, WERE REGULATED BY DIFFERENTIALLY EXPRESSED HEPATIC AND SPERMATOZOAL MIRNAS AND LNCRNAS IN BREEDER COCKS AND BROILER OFFSPRING. MOREOVER, THE EXPRESSION OF ANGPTL4 COULD ALSO BE REGULATED BY DIFFERENTIALLY EXPRESSED MIRNAS AND LNCRNAS IN SPERMATOZOA VIA COMPETITIVE ENDOGENOUS RNA (CERNA) MECHANISMS. OVERALL, THIS MODEL SUGGESTS THAT PATERNAL FOLATE COULD TRANSGENERATIONALLY REGULATE LIPID AND GLUCOSE METABOLISM IN BROILER OFFSPRING AND THE EPIGENETIC TRANSMISSION MAY INVOLVE ALTERED SPERMATOZOAL MIRNAS AND LNCRNAS. 2019 3 1263 32 CYCLIC VARIATIONS IN INCUBATION CONDITIONS INDUCE ADAPTIVE RESPONSES TO LATER HEAT EXPOSURE IN CHICKENS: A REVIEW. SELECTION PROGRAMS HAVE ENABLED BROILER CHICKENS TO GAIN MUSCLE MASS WITHOUT SIMILAR ENLARGEMENT OF THE CARDIOVASCULAR AND RESPIRATORY SYSTEMS THAT ARE ESSENTIAL FOR THERMOREGULATORY EFFICIENCY. MEAT-TYPE CHICKENS COPE WITH HIGH AMBIENT TEMPERATURE BY REDUCING FEED INTAKE AND GROWTH DURING CHRONIC AND MODERATE HEAT EXPOSURE. IN CASE OF ACUTE HEAT EXPOSURE, A DRAMATIC INCREASE IN MORBIDITY AND MORTALITY CAN OCCUR. IN ORDER TO ALLEVIATE HEAT STRESS IN THE LONG TERM, RESEARCH HAS RECENTLY FOCUSED ON EARLY THERMAL MANIPULATION. AIMED AT STIMULATION OF LONG-TERM THERMOTOLERANCE, THE THERMAL MANIPULATION OF EMBRYOS IS A METHOD BASED ON FINE TUNING OF INCUBATION CONDITIONS, TAKING INTO ACCOUNT THE LEVEL AND DURATION OF INCREASES IN TEMPERATURE AND RELATIVE HUMIDITY DURING A CRITICAL PERIOD OF EMBRYOGENESIS. THE CONSEQUENCES OF THERMAL MANIPULATION ON THE PERFORMANCE AND MEAT QUALITY OF BROILER CHICKENS HAVE BEEN EXPLORED TO ENSURE THE POTENTIAL APPLICATION OF THIS STRATEGY. THE PHYSIOLOGICAL BASIS OF THE METHOD IS THE INDUCTION OF EPIGENETIC AND METABOLIC MECHANISMS THAT CONTROL BODY TEMPERATURE IN THE LONG TERM. EARLY THERMAL MANIPULATION CAN ENHANCE POULTRY RESISTANCE TO ENVIRONMENTAL CHANGES WITHOUT MUCH EFFECT ON GROWTH PERFORMANCE. THIS REVIEW PRESENTS THE MAIN STRATEGIES OF EARLY HEAT EXPOSURE AND THE PHYSIOLOGICAL CONCEPTS ON WHICH THESE METHODS WERE BASED. THE CELLULAR MECHANISMS POTENTIALLY UNDERLYING THE ADAPTIVE RESPONSE ARE DISCUSSED AS WELL AS THE POTENTIAL INTEREST OF THERMAL MANIPULATION OF EMBRYOS FOR POULTRY PRODUCTION. 2015 4 544 30 ATTAINMENT OF THERMOREGULATION AS AFFECTED BY ENVIRONMENTAL FACTORS. THE REVIEW ADDRESSES THE DEVELOPMENT OF THERMOREGULATION IN POULTRY EMBRYOS AS WELL AS THE EFFECT OF ACUTE AND CHRONIC CHANGES OF ENVIRONMENTAL FACTORS ON THIS PROCESS AND THE INCUBATION TEMPERATURE BEING THE FOREMOST. IN POULTRY, THE EARLY DEVELOPMENT OF ADAPTIVE BODY FUNCTIONS, LIKE THE THERMOREGULATORY SYSTEM, IS CHARACTERIZED BY THE FOLLOWING PECULIARITIES. FIRST, THE DEVELOPMENT OF PERIPHERAL AS WELL AS CENTRAL NERVOUS THERMOREGULATORY MECHANISMS START DURING THE PRENATAL ONTOGENY. HOWEVER, THEIR MATURITY IS ATTAINED DURING EARLY POSTNATAL DEVELOPMENT. IN THE PERINATAL PERIOD, ENVIRONMENTAL FACTORS HAVE A HIGH EFFECT ON DEVELOPMENT OF TEMPERATURE REGULATION. SECOND, ACUTE CHANGES IN THE ENVIRONMENTAL CONDITIONS INDUCE AS A RULE FIRST UNCOORDINATED AND IMMEDIATELY NONADAPTIVE REACTIONS. LATER, THE UNCOORDINATED NONADAPTIVE REACTIONS CHANGE INTO COORDINATED (ADAPTIVE) REACTIONS. PRENATAL ENVIRONMENTAL INFLUENCES MAY HAVE A TRAINING EFFECT ON THE POSTNATAL EFFICIENCY OF THE THERMO-REGULATORY SYSTEM. THIRD, FUNCTIONAL SYSTEMS OF THE ORGANISM DEVELOP FROM AN OPEN LOOP SYSTEM WITHOUT FEEDBACK CONTROL INTO A CLOSED SYSTEM CONTROLLED BY A FEEDBACK MECHANISM. DURING THIS CRITICAL PERIOD, THE ACTUAL ENVIRONMENT MODULATES THE DEVELOPMENT OF THE RESPECTIVE PHYSIOLOGICAL CONTROL SYSTEMS FOR THE ENTIRE LIFE PERIOD, ESPECIALLY BY CHANGES IN NEUROORGANIZATION AND EXPRESSION OF RELATED EFFECTOR GENES. KNOWLEDGE ON THESE MECHANISMS MIGHT BE SPECIFICALLY USED TO GENERATE LONG-TERM ADAPTATION OF THE ORGANISM TO THE POSTNATAL CLIMATIC CONDITIONS (PERINATAL EPIGENETIC TEMPERATURE ADAPTATION). IN POULTRY, PERINATAL EPIGENETIC TEMPERATURE ADAPTATION WAS DEVELOPED BY CHANGES IN THE INCUBATION TEMPERATURE. WHEN A COMPARISON IS MADE IN BIRDS, WHICH WERE INCUBATED AT 37.5 DEGREES C, A LOW INCUBATION TEMPERATURE INDUCED POSTNATAL COLD ADAPTATION, AND WARM INCUBATION TEMPERATURE INDUCED POSTNATAL HEAT ADAPTATION. PERINATAL EPIGENETIC TEMPERATURE ADAPTATION EXHIBITED CHANGES IN THE NEURONAL THERMOSENSITIVITY IN THE HYPOTHALAMUS AS WELL AS IN THE PERIPHERAL THERMOREGULATORY MECHANISMS. THESE ALTERATIONS COULD BE ALREADY FOUND AT THE END OF INCUBATION. FURTHER, TEMPERATURE-EXPERIENCED EMBRYOS HAVE A LOWER C-FOS EXPRESSION THAN IN THE CONTROL AFTER ACUTE HEAT STRESS. 2007 5 3713 39 INHERITANCE OF ACQUIRED BEHAVIOUR ADAPTATIONS AND BRAIN GENE EXPRESSION IN CHICKENS. BACKGROUND: ENVIRONMENTAL CHALLENGES MAY AFFECT BOTH THE EXPOSED INDIVIDUALS AND THEIR OFFSPRING. WE INVESTIGATED POSSIBLE ADAPTIVE ASPECTS OF SUCH CROSS-GENERATION TRANSMISSIONS, AND HYPOTHESIZED THAT CHRONIC UNPREDICTABLE FOOD ACCESS WOULD CAUSE CHICKENS TO SHOW A MORE CONSERVATIVE FEEDING STRATEGY AND TO BE MORE DOMINANT, AND THAT THESE ADAPTATIONS WOULD BE TRANSMITTED TO THE OFFSPRING. METHODOLOGY/PRINCIPAL FINDINGS: PARENTS WERE RAISED IN AN UNPREDICTABLE (UL) OR IN PREDICTABLE DIURNAL LIGHT RHYTHM (PL, 12:12 H LIGHT:DARK). IN A FORAGING TEST, UL BIRDS PECKED MORE AT FREELY AVAILABLE, RATHER THAN AT HIDDEN AND MORE ATTRACTIVE FOOD, COMPARED TO BIRDS FROM THE PL GROUP. FEMALE OFFSPRING OF UL BIRDS, RAISED IN PREDICTABLE LIGHT CONDITIONS WITHOUT PARENTAL CONTACT, SHOWED A SIMILAR FORAGING BEHAVIOR, DIFFERING FROM OFFSPRING OF PL BIRDS. FURTHERMORE, ADULT OFFSPRING OF UL BIRDS PERFORMED MORE FOOD PECKS IN A DOMINANCE TEST, SHOWED A HIGHER PREFERENCE FOR HIGH ENERGY FOOD, SURVIVED BETTER, AND WERE HEAVIER THAN OFFSPRING OF PL PARENTS. USING CDNA MICROARRAYS, WE FOUND THAT THE DIFFERENTIAL BRAIN GENE EXPRESSION CAUSED BY THE CHALLENGE WAS MIRRORED IN THE OFFSPRING. IN PARTICULAR, SEVERAL IMMUNOGLOBULIN GENES SEEMED TO BE AFFECTED SIMILARLY IN BOTH UL PARENTS AND THEIR OFFSPRING. ESTRADIOL LEVELS WERE SIGNIFICANTLY HIGHER IN EGG YOLK FROM UL BIRDS, SUGGESTING ONE POSSIBLE MECHANISM FOR THESE EFFECTS. CONCLUSIONS/SIGNIFICANCE: OUR FINDINGS SUGGEST THAT UNPREDICTABLE FOOD ACCESS CAUSED SEEMINGLY ADAPTIVE RESPONSES IN FEEDING BEHAVIOR, WHICH MAY HAVE BEEN TRANSMITTED TO THE OFFSPRING BY MEANS OF EPIGENETIC MECHANISMS, INCLUDING REGULATION OF IMMUNE GENES. THIS MAY HAVE PREPARED THE OFFSPRING FOR COPING WITH AN UNPREDICTABLE ENVIRONMENT. 2009 6 4946 25 PATERNAL PSYCHOLOGICAL STRESS REPROGRAMS HEPATIC GLUCONEOGENESIS IN OFFSPRING. BOTH EPIDEMIOLOGIC AND EXPERIMENTAL ANIMAL STUDIES DEMONSTRATE THAT CHRONIC PSYCHOLOGICAL STRESS EXERTS ADVERSE EFFECTS ON THE INITIATION AND/OR PROGRESSION OF MANY DISEASES. HOWEVER, INTERGENERATIONAL EFFECTS OF THIS ENVIRONMENTAL INFORMATION REMAINS POORLY UNDERSTOOD. HERE, USING A C57BL/6 MOUSE MODEL OF RESTRAINT STRESS, WE SHOW THAT OFFSPRING OF STRESSED FATHERS EXHIBIT HYPERGLYCEMIA DUE TO ENHANCED HEPATIC GLUCONEOGENESIS AND ELEVATED EXPRESSION OF PEPCK. MECHANISTICALLY, WE IDENTIFY AN EPIGENETIC ALTERATION AT THE PROMOTER REGION OF THE SFMBT2 GENE, A MATERNALLY IMPRINTED POLYCOMB GENE, LEADING TO A DOWNREGULATION OF INTRONIC MICRORNA-466B-3P, WHICH POST-TRANSCRIPTIONALLY INHIBITS PEPCK EXPRESSION. IMPORTANTLY, HYPERGLYCEMIA IN F1 MICE IS REVERSED BY RU486 TREATMENT IN FATHERS, AND DEXAMETHASONE ADMINISTRATION IN F0 MICE PHENOCOPIES THE ROLES OF RESTRAINT STRESS. THUS, WE PROVIDE EVIDENCE SHOWING THE EFFECTS OF PATERNAL PSYCHOLOGICAL STRESS ON THE REGULATION OF GLUCOSE METABOLISM IN OFFSPRING, WHICH MAY HAVE PROFOUND IMPLICATIONS FOR OUR UNDERSTANDING OF HEALTH AND DISEASE RISK INHERITED FROM FATHERS. 2016 7 3300 27 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 8 3816 31 INTRAUTERINE PROGRAMMING OF CARTILAGINOUS 11BETA-HSD2 INDUCED BY CORTICOSTERONE AND CAFFEINE MEDIATED SUSCEPTIBILITY TO ADULT OSTEOARTHRITIS. OUR PREVIOUS STUDY REPORTED THAT PRENATAL CAFFEINE EXPOSURE (PCE) COULD INDUCE CHONDRODYSPLASIA AND INCREASE THE SUSCEPTIBILITY TO OSTEOARTHRITIS IN OFFSPRING RATS. HOWEVER, THE POTENTIAL MECHANISMS AND INITIATING FACTORS REMAIN UNKNOWN. THIS STUDY AIMS TO INVESTIGATE WHETHER 11BETA-HSD2, A GLUCOCORTICOID-METABOLIZING ENZYME, IS INVOLVED IN THE SUSCEPTIBILITY OF OSTEOARTHRITIS INDUCED BY PCE AND TO FURTHER EXPLORE ITS POTENTIAL MECHANISMS AND INITIATING FACTORS. FIRSTLY, WE FOUND THAT PCE REDUCED CARTILAGE MATRIX SYNTHESIS (AGGRECAN/COL2A1 EXPRESSION) IN MALE ADULT OFFSPRING RATS AND EXHIBITED AN OSTEOARTHRITIS PHENOTYPE FOLLOWING CHRONIC STRESS, WHICH WAS ASSOCIATED WITH PERSISTENTLY REDUCED H3K9AC AND H3K27AC LEVELS AT THE PROMOTER OF 11BETA-HSD2 AS WELL AS ITS EXPRESSION IN THE CARTILAGE FROM FETUS TO ADULTHOOD. THE EXPRESSION OF 11BETA-HSD2, AGGRECAN AND COL2A1 WERE ALL DECREASED BY CORTICOSTERONE IN THE FETAL CHONDROCYTES, WHILE OVEREXPRESSION OF 11BETA-HSD2 COULD PARTIALLY ALLEVIATE THE DECREASE OF MATRIX SYNTHESIS INDUCED BY CORTICOSTERONE IN VITRO. FURTHERMORE, THE GLUCOCORTICOID RECEPTOR (GR) ACTIVATED BY GLUCOCORTICOIDS DIRECTLY BONDED TO THE PROMOTER REGION OF 11BETA-HSD2 TO INHIBIT ITS EXPRESSION. MEANWHILE, THE ACTIVATED GR REDUCED THE H3K9AC AND H3K27AC LEVELS OF 11BETA-HSD2 BY RECRUITING HDAC4 AND PROMOTING GR-HDAC4 PROTEIN INTERACTION TO INHIBIT THE 11BETA-HSD2 EXPRESSION. MOREOVER, CAFFEINE COULD REDUCE THE EXPRESSION OF 11BETA-HSD2 BY INHIBITING THE CAMP/PKA SIGNALING PATHWAY BUT WITHOUT REDUCING THE H3K9AC AND H3K27AC LEVELS OF 11BETA-HSD2, THEREBY SYNERGISTICALLY ENHANCING THE CORTICOSTERONE EFFECT. IN CONCLUSION, THE PERSISTENTLY REDUCED H3K9AC AND H3K27AC LEVELS OF 11BETA-HSD2 FROM FETUS TO ADULTHOOD MEDIATED THE INHIBITION OF CARTILAGE MATRIX SYNTHESIS AND THE INCREASED SUSCEPTIBILITY TO OSTEOARTHRITIS. THIS EPIGENETIC PROGRAMMING CHANGE IN UTERO WAS INDUCED BY GLUCOCORTICOIDS WITH SYNERGISTIC EFFECT OF CAFFEINE. 2022 9 2173 38 EPIGENETIC MECHANISMS INVOLVED IN INTRAUTERINE GROWTH RESTRICTION AND ABERRANT KIDNEY DEVELOPMENT AND FUNCTION. INTRAUTERINE GROWTH RESTRICTION (IUGR) DUE TO UTEROPLACENTAL INSUFFICIENCY RESULTS IN A PLACENTA THAT IS UNABLE TO PROVIDE ADEQUATE NUTRIENTS AND OXYGEN TO THE FETUS. THESE GROWTH-RESTRICTED BABIES HAVE AN INCREASED RISK OF HYPERTENSION AND CHRONIC KIDNEY DISEASE LATER IN LIFE. IN RATS, BOTH MALE AND FEMALE GROWTH-RESTRICTED OFFSPRING HAVE NEPHRON DEFICITS BUT ONLY MALES DEVELOP KIDNEY DYSFUNCTION AND HIGH BLOOD PRESSURE. IN ADDITION, THERE IS TRANSGENERATIONAL TRANSMISSION OF NEPHRON DEFICITS AND HYPERTENSION RISK. THEREFORE, EPIGENETIC MECHANISMS MAY EXPLAIN THE SEX-SPECIFIC PROGRAMMING AND MULTIGENERATIONAL TRANSMISSION OF IUGR-RELATED PHENOTYPES. EXPRESSION OF DNA METHYLTRANSFERASES (DNMT1AND DNMT3A) AND IMPRINTED GENES (PEG3, SNRPN, KCNQ1, AND CDKN1C) WERE INVESTIGATED IN KIDNEY TISSUES OF SHAM AND IUGR RATS IN F1 (EMBRYONIC DAY 20 (E20) AND POSTNATAL DAY 1 (PN1)) AND F2 (6 AND 12 MONTHS OF AGE, PATERNAL AND MATERNAL LINES) GENERATIONS (N = 6-13/GROUP). IN COMPARISON TO SHAM OFFSPRING, F1 IUGR RATS HAD A 19% DECREASE IN DNMT3A EXPRESSION AT E20 (P < 0.05), WITH DECREASED CDKN1C (19%, P < 0.05) AND INCREASED KCNQ1 (1.6-FOLD, P < 0.01) AT PN1. THERE WAS A SEX-SPECIFIC DIFFERENCE IN CDKN1C AND SNRPN EXPRESSION AT E20, WITH 29% AND 34% HIGHER EXPRESSION IN IUGR MALES COMPARED TO FEMALES, RESPECTIVELY (P < 0.05). PEG3 SEX-SPECIFIC EXPRESSION WAS LOST IN THE F2 IUGR OFFSPRING, ONLY IN THE MATERNAL LINE. THESE FINDINGS SUGGEST THAT EPIGENETIC MECHANISMS MAY BE ALTERED IN RENAL EMBRYONIC AND/OR FETAL DEVELOPMENT IN GROWTH-RESTRICTED OFFSPRING, WHICH COULD ALTER KIDNEY FUNCTION, PREDISPOSING THESE OFFSPRING TO KIDNEY DISEASE LATER IN LIFE. 2021 10 1839 37 EFFECTS OF PRENATAL NICOTINE EXPOSURE ON HEPATIC GLUCOSE AND LIPID METABOLISM IN OFFSPRING RATS AND ITS HEREDITABILITY. PRENATAL NICOTINE EXPOSURE (PNE) COULD INDUCE AN INCREASED SUSCEPTIBILITY TO MULTIPLE CHRONIC DISEASES IN ADULT OFFSPRING, THAT MAINLY CAUSED BY INTRAUTERINE MATERNAL GLUCOCORTICOID (GC) OVER-EXPOSURE. WE INVESTIGATED THE CHANGES AND INHERITABILITY OF HEPATIC GLUCOSE AND LIPID METABOLISM CAUSED BY PNE, TO DECIPHER THE POSSIBLE INTRAUTERINE PROGRAMMING MECHANISM. PREGNANT WISTAR RATS WERE ADMINISTERED SUBCUTANEOUSLY WITH 2 MG/KG.D NICOTINE FROM GESTATIONAL DAY (GD) 9 APPROXIMATELY 20, AND SECOND-GENERATION (F2) WERE SET ACCORDING TO THE MATING BETWEEN CONTROL FEMALES AND PNE MALES. THE RESULTS SHOWED THAT SERUM PHENOTYPES AND HEPATIC ENZYMES OF GLUCOSE AND LIPID METABOLISM WERE LOWER IN F1 FETAL RATS OF PNE BUT HIGHER IN THE F1 ADULT RATS. MEANWHILE, THE ACTIVATED STATES OF HEPATIC GLUCOCORTICOID-ACTIVATION SYSTEM, INCLUDING TYPE 1 AND TYPE 2 11BETA-HYDROXYSTEROID DEHYDROGENASES (HSD11B1/2), NUCLEAR RECEPTOR SUBFAMILY 3, GROUP C, MEMBER 1 (NR3C1) AND CCAAT ENHANCER BINDING PROTEIN ALPHA (CEBPA), WERE POSITIVELY CORRELATED WITH SERUM CORTICOSTERONE LEVELS BUT NEGATIVELY CORRELATED WITH THE HISTONE ACETYLATION (H3K27AC) AND EXPRESSION LEVELS OF INSULIN-LIKE GROWTH FACTOR 1 (IGF1) BEFORE AND AFTER BIRTH. FURTHERMORE, SERUM PHENOTYPES AND HEPATIC ENZYMES OF GLUCOSE AND LIPID METABOLISM WERE LOWER IN BOTH F2 FETAL AND ADULT RATS OF PNE, WHICH WERE CONSISTENT WITH THE HEPATIC CHANGES OF GC-IGF1 AXIS AND THE GLUCOCORTICOID-ACTIVATION SYSTEM. IN CONCLUSION, PNE COULD LEAD TO INHERITABLE CHANGES OF HEPATIC GLUCOSE AND LIPID METABOLISM, WHICH ARE RELATED TO THE INTRAUTERINE PROGRAMMING OF GC-IGF1 AXIS INDUCED BY THE GLUCOCORTICOID-ACTIVATION SYSTEM. 2020 11 5090 32 PLACENTAL ADIPONECTIN GENE DNA METHYLATION LEVELS ARE ASSOCIATED WITH MOTHERS' BLOOD GLUCOSE CONCENTRATION. GROWING EVIDENCE SUGGESTS THAT EPIGENETIC PROFILE CHANGES OCCURRING DURING FETAL DEVELOPMENT IN RESPONSE TO IN UTERO ENVIRONMENT VARIATIONS COULD BE ONE OF THE MECHANISMS INVOLVED IN THE EARLY DETERMINANTS OF ADULT CHRONIC DISEASES. IN THIS STUDY, WE TESTED WHETHER MATERNAL GLYCEMIC STATUS IS ASSOCIATED WITH THE ADIPONECTIN GENE (ADIPOQ) DNA METHYLATION PROFILE IN PLACENTA TISSUE, IN MATERNAL CIRCULATING BLOOD CELLS, AND IN CORD BLOOD CELLS. WE FOUND THAT LOWER DNA METHYLATION LEVELS IN THE PROMOTER OF ADIPOQ ON THE FETAL SIDE OF THE PLACENTA WERE CORRELATED WITH HIGHER MATERNAL GLUCOSE LEVELS DURING THE SECOND TRIMESTER OF PREGNANCY (2-H GLUCOSE AFTER THE ORAL GLUCOSE TOLERANCE TEST; R(S)