1  4723 96 NONHUMAN PRIMATE MODELS OF POLYCYSTIC OVARY SYNDROME. WITH CLOSE GENOMIC AND PHENOTYPIC SIMILARITY TO HUMANS, NONHUMAN PRIMATE MODELS PROVIDE COMPREHENSIVE EPIGENETIC MIMICS OF POLYCYSTIC OVARY SYNDROME (PCOS), SUGGESTING EARLY LIFE TARGETING FOR PREVENTION. FETAL EXPOSURE TO TESTOSTERONE (T), OF ALL NONHUMAN PRIMATE EMULATIONS, PROVIDES THE CLOSEST PCOS-LIKE PHENOTYPES, WITH EARLY-TO-MID GESTATION T-EXPOSED FEMALE RHESUS MONKEYS EXHIBITING ADULT REPRODUCTIVE, ENDOCRINOLOGICAL AND METABOLIC DYSFUNCTIONAL TRAITS THAT ARE CO-PATHOLOGIES OF PCOS. LATE GESTATIONAL T EXPOSURE, WHILE INDUCING ADULT OVARIAN HYPERANDROGENISM AND MENSTRUAL ABNORMALITIES, HAS LESS DYSFUNCTIONAL METABOLIC ACCOMPANIMENT. FETAL EXPOSURES TO DIHYDROTESTOSTERONE (DHT) OR DIETHYLSTILBESTROL (DES) SUGGEST ANDROGENIC AND ESTROGENIC ASPECTS OF FETAL PROGRAMMING. NEONATAL EXPOSURE TO T PRODUCES NO PCOS-LIKE OUTCOME, WHILE CONTINUOUS T TREATMENT OF JUVENILE FEMALES CAUSES PRECOCIOUS WEIGHT GAIN AND EARLY MENARCHE (HIGH T), OR HIGH LH AND WEIGHT GAIN (MODERATE T). ACUTE T EXPOSURE OF ADULT FEMALES GENERATES POLYFOLLICULAR OVARIES, WHILE CHRONIC T EXPOSURE INDUCES SUBTLE MENSTRUAL IRREGULARITIES WITHOUT METABOLIC DYSFUNCTION.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
2  5191 18 PRENATAL DEXAMETHASONE EXPOSURE PROGRAMS THE DECREASED TESTOSTERONE SYNTHESIS IN OFFSPRING RATS BY LOW LEVEL OF ENDOGENOUS GLUCOCORTICOIDS. PRENATAL DEXAMETHASONE EXPOSURE (PDE) CAN DECREASE MATERNAL ENDOGENOUS GLUCOCORTICOID LEVEL AND INDUCE TESTICULAR DYSPLASIA IN MALE OFFSPRING RATS. IN THIS STUDY WE INVESTIGATED LOW LEVEL ENDOGENOUS GLUCOCORTICOID-MEDIATED TESTICULAR DYSPLASIA IN PDE OFFSPRING AND ELUCIDATED THE INTRAUTERINE EPIGENETIC PROGRAMMING MECHANISMS. PREGNANT RATS WERE INJECTED WITH DEXAMETHASONE (0.2 MG.KG(-1).D(-1), SC) ON GESTATIONAL DAY (GD) 9-20. THE OFFSPRING RAT BLOOD AND TESTIS WERE COLLECTED AFTER EUTHANASIA ON GD20, POSTNATAL WEEK (PW) 12 OR PW28. WE SHOWED THAT PDE INDUCED ABNORMAL MORPHOLOGY OF TESTIS AND SIGNIFICANTLY DECREASED THE EXPRESSION OF TESTOSTERONE SYNTHESIS-RELATED GENES AS WELL AS TESTOSTERONE PRODUCTION BEFORE AND AFTER BIRTH. MEANWHILE, SERUM CORTICOSTERONE, THE EXPRESSION AND HISTONE 3 LYSINE 14 ACETYLATION (H3K14AC) OF TESTICULAR INSULIN-LIKE GROWTH FACTOR 1 (IGF1) WERE SIGNIFICANTLY DECREASED. AFTER THE PREGNANT RATS WERE SUBJECTED TO CHRONIC STRESS FOR 2 WEEKS (PW10-12), SERUM CORTICOSTERONE LEVEL WAS INCREASED IN THE ADULT PDE OFFSPRING, AND THE ABOVE-MENTIONED OTHER INDICATORS WERE ALSO IMPROVED. CULTURED LEYDIG CELLS (TM3) WERE TREATED WITH CORTICOSTERONE (62.5-500 NM) IN VITRO. WE SHOWED THAT CORTICOSTERONE CONCENTRATION-DEPENDENTLY INHIBITED GLUCOCORTICOID RECEPTOR ALPHA (GRALPHA) AND MIR-124-3P EXPRESSION, INCREASED HISTONE DEACETYLASE 5 (HDAC5) EXPRESSION, AND DECREASED IGF1 H3K14AC LEVEL AND THE EXPRESSION OF IGF1/STEROIDOGENIC ACUTE REGULATORY PROTEIN (STAR), SUGGESTING THAT CORTICOSTERONE AT LOWER THAN PHYSIOLOGICAL LEVEL (<500 NM) INHIBITED TESTOSTERONE SYNTHESIS BY REDUCING H3K14AC AND THE EXPRESSION LEVEL OF IGF1 THROUGH GRALPHA/MIR-124-3P/HDAC5 PATHWAY. IN CONCLUSION, PDE CAN CAUSE PERSISTENT INHIBITION OF TESTOSTERONE SYNTHESIS BEFORE AND AFTER BIRTH IN THE OFFSPRING RATS BY LOW LEVEL OF ENDOGENOUS GLUCOCORTICOIDS.	2022	
                                                                                                                                                                                                                                                                                                                              
3   369 25 AN ANDROGEN-DEPENDENT SEXUAL DIMORPHISM VISIBLE AT PUBERTY IN THE RAT HYPOTHALAMUS. MORPHOLOGICAL STUDIES IN RODENTS HAVE WELL DOCUMENTED THE MASCULINIZATION OF THE PERINATAL BRAIN BY ESTRADIOL DERIVED FROM AROMATIZED TESTOSTERONE, AND THE RESULTING IRREVERSIBLE QUANTITATIVE SEX-DIFFERENCES GENERATED IN CELL NUMBERS OR EXPRESSION OF CHEMICAL PHENOTYPES. HERE, USING IMMUNOHISTOCHEMISTRY, WE EXPLORED HOW THIS APPLIES TO THE POSTNATAL DEVELOPMENT AND MASCULINIZATION OF THE NEUROKININ B (NKB)-CONTAINING SYSTEM OF THE ARCUATE NUCLEUS/MEDIAN EMINENCE COMPLEX (ARC/ME). IN ADULT RATS, NKB-IMMUNOREACTIVE NEURONS EXHIBIT AN UNUSUAL, QUALITATIVE SEXUAL DIMORPHISM OF THEIR VENTRAL AXONAL PROJECTIONS: TO THE NEUROPIL IN FEMALES, TO CAPILLARY VESSELS IN MALES. IN ADULTS, THERE WAS NO SEX-DIFFERENCE IN THE NUMBERS OF NKB-IMMUNOREACTIVE PERIKARYA OR CAPILLARY VESSELS IN THE ARC/ME, SUGGESTING THAT THIS SEXUAL DIMORPHISM CANNOT BE EXPLAINED BY THE EXISTENCE OF SUPERNUMERARY STRUCTURES. AT BIRTH (DAY 0) THE NKB SYSTEM WAS IMMATURE IN BOTH SEXES, AND WHILE ITS ADULT FEATURES EMERGED PROGRESSIVELY UNTIL PUBERTY IN FEMALES, THEY DID NOT DEVELOP BEFORE PUBERTY (DAY 40) IN MALES, REVEALING A SEXUAL DIMORPHISM ONLY LATE POSTNATALLY. WHEN MALES WERE ORCHIDECTOMIZED AT DAY 30, THE MASCULINE DISTRIBUTION OF NKB-IMMUNOREACTIVE AXONS EXPECTED AT DAY 40 WAS NOT SEEN, WHILE IT WAS APPARENT AFTER CHRONIC TREATMENT WITH TESTOSTERONE OR DIHYDROTESTOSTERONE, SUGGESTING A TESTICULAR MASCULINIZING ACTION VIA ANDROGEN RECEPTORS AT PUBERTY. MOREOVER IN THESE PREPUBERTAL-ORCHIDECTOMIZED MALES, THE DISTRIBUTION OF NKB-IMMUNOREACTIVE AXONS WAS SURPRISINGLY FEMINIZED BY CHRONIC ESTRADIOL ALONE, SUGGESTING THAT NKB NEURONS ARE NOT IRREVERSIBLY PROGRAMMED BEFORE PUBERTY. LAST, IN ADULT FEMALES, THE DISTRIBUTION OF NKB-IMMUNOREACTIVE AXONS WAS FEMININE 30 DAYS AFTER OVARIECTOMY, AND IT WAS MASCULINIZED AFTER CONCURRENT CHRONIC DIHYDROTESTOSTERONE, SUGGESTING THAT NKB NEURONS REMAIN RESPONSIVE TO ANDROGENS LATE IN REPRODUCTIVE LIFE. THUS, THE SEXUAL DIFFERENTIATION OF THE HYPOTHALAMUS PROCEEDS WELL BEYOND THE PERINATAL PERIOD AND INCLUDES THE EPIGENETIC ACTION OF NON-AROMATIZABLE ANDROGENS UPON SUBSETS OF NEURONS THAT HAVE RETAINED BIPOTENT FEATURES.	2007	
                                                                                  
4  5970 10 TESTOSTERONE ACTS WITHIN THE MEDIAL AMYGDALA OF RATS TO REDUCE INNATE FEAR TO PREDATOR ODOR AKIN TO THE EFFECTS OF TOXOPLASMA GONDII INFECTION. RATS INFECTED WITH THE PROTOZOAN TOXOPLASMA GONDII EXHIBIT A REDUCED AVERSION TO CAT ODOR. THIS BEHAVIORAL CHANGE IS THOUGHT TO INCREASE TROPHIC TRANSMISSION OF THE PARASITE. INFECTED MALE RATS ALSO SHOW A GREATER TESTICULAR SYNTHESIS OF TESTOSTERONE AND EPIGENETIC CHANGE IN ARGININE VASOPRESSIN WITHIN THE MEDIAL AMYGDALA. HERE, WE SHOW THAT EXOGENOUS SUPPLY OF TESTOSTERONE WITHIN MEA OF UNINFECTED CASTRATES RECAPITULATES REDUCTION IN INNATE FEAR AKIN TO BEHAVIORAL CHANGE ATTRIBUTED TO THE PARASITE. WE ALSO SHOW THAT CASTRATION POST ESTABLISHMENT OF CHRONIC INFECTION PRECLUDES CHANGES IN FEAR AND MEDIAL AMYGDALA ARGININE VASOPRESSIN IN THE INFECTED MALE RATS. THESE OBSERVATIONS SUPPORT THE ROLE OF GONADAL HORMONES AND PURSUANT NEUROENDOCRINE CHANGES IN MEDIATING THE LOSS OF FEAR IN THE INFECTED RATS. THIS WORK ALSO DEMONSTRATES THAT TESTOSTERONE ACTING SPECIFICALLY WITHIN THE MEDIAL AMYGDALA SUFFICIENTLY EXPLAINS REDUCED DEFENSIVE BEHAVIORS OFTEN OBSERVED DURING THE APPETITIVE COMPONENT OF REPRODUCTIVE BEHAVIORS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
5  4068 23 MATERNAL ANDROGEN EXCESS AND OBESITY INDUCE SEXUALLY DIMORPHIC ANXIETY-LIKE BEHAVIOR IN THE OFFSPRING. MATERNAL POLYCYSTIC OVARY SYNDROME (PCOS), A CONDITION ASSOCIATED WITH HYPERANDROGENISM, IS SUGGESTED TO INCREASE ANXIETY-LIKE BEHAVIOR IN THE OFFSPRING. BECAUSE PCOS IS CLOSELY LINKED TO OBESITY, WE INVESTIGATED THE IMPACT OF AN ADVERSE HORMONAL OR METABOLIC MATERNAL ENVIRONMENT AND OFFSPRING OBESITY ON ANXIETY IN THE OFFSPRING. THE OBESE PCOS PHENOTYPE WAS INDUCED BY CHRONIC HIGH-FAT-HIGH-SUCROSE (HFHS) CONSUMPTION TOGETHER WITH PRENATAL DIHYDROTESTOSTERONE EXPOSURE IN MOUSE DAMS. ANXIETY-LIKE BEHAVIOR WAS ASSESSED IN ADULT OFFSPRING WITH THE ELEVATED-PLUS MAZE AND OPEN-FIELD TESTS. THE INFLUENCE OF MATERNAL ANDROGENS AND MATERNAL AND OFFSPRING DIET ON GENES IMPLICATED IN ANXIETY WERE ANALYZED IN THE AMYGDALA AND HYPOTHALAMUS WITH REAL-TIME PCR ( N = 47). INDEPENDENT OF DIET, FEMALE OFFSPRING EXPOSED TO MATERNAL ANDROGENS WERE MORE ANXIOUS AND DISPLAYED UP-REGULATION OF ADRENOCEPTOR ALPHA 1B IN THE AMYGDALA AND UP-REGULATION OF HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE ( CRH). BY CONTRAST, MALE OFFSPRING EXPOSED TO A HFHS MATERNAL DIET HAD INCREASED ANXIETY-LIKE BEHAVIOR AND SHOWED UP-REGULATION OF EPIGENETIC MARKERS IN THE AMYGDALA AND UP-REGULATION OF HYPOTHALAMIC CRH. OVERALL, THERE WERE SUBSTANTIAL SEX DIFFERENCES IN GENE EXPRESSION IN THE BRAIN. THESE FINDINGS PROVIDE NOVEL INSIGHT INTO HOW MATERNAL ANDROGENS AND OBESITY EXERT SEX-SPECIFIC EFFECTS ON BEHAVIOR AND GENE EXPRESSION IN THE OFFSPRING OF A PCOS MOUSE MODEL.-MANTI, M., FORNES, R., QI, X., FOLMERZ, E., LINDEN HIRSCHBERG, A., DE CASTRO BARBOSA, T., MALIQUEO, M., BENRICK, A., STENER-VICTORIN, E. MATERNAL ANDROGEN EXCESS AND OBESITY INDUCE SEXUALLY DIMORPHIC ANXIETY-LIKE BEHAVIOR IN THE OFFSPRING.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
6   936 14 CHRONIC LOW-LEVEL PERFLUOROOCTANE SULFONATE (PFOS) EXPOSURE PROMOTES TESTICULAR STEROIDOGENESIS THROUGH ENHANCED HISTONE ACETYLATION. PERFLUOROOCTANE SULFONATE (PFOS), AN ARTIFICIAL PERFLUORINATED COMPOUND, HAS BEEN ASSOCIATED WITH MALE REPRODUCTIVE DISORDERS. HISTONE MODIFICATIONS ARE IMPORTANT EPIGENETIC MEDIATORS; HOWEVER, THE IMPACT OF PFOS EXPOSURE ON TESTICULAR STEROIDOGENESIS THROUGH HISTONE MODIFICATION REGULATIONS REMAINS TO BE ELUCIDATED. IN THIS STUDY, WE EXAMINED THE ROLES OF HISTONE MODIFICATIONS IN REGULATING STEROID HORMONE PRODUCTION IN MALE RATS CHRONICALLY EXPOSED TO LOW-LEVEL PFOS. THE RESULTS INDICATE THAT PFOS EXPOSURE SIGNIFICANTLY UP-REGULATED THE EXPRESSIONS OF STAR, CYP11A1 AND 3BETA-HSD, WHILE CYP17A1 AND 17BETA-HSD WERE DOWN-REGULATED, THUS CONTRIBUTING TO THE ELEVATED PROGESTERONE AND TESTOSTERONE LEVELS. FURTHERMORE, PFOS SIGNIFICANTLY INCREASED THE HISTONES H3K9ME2, H3K9AC AND H3K18AC WHILE REDUCED H3K9ME3 IN RAT TESTIS. IT IS KNOWN THAT HISTONE MODIFICATIONS ARE CLOSELY INVOLVED IN GENE TRANSCRIPTION. THEREFORE, TO INVESTIGATE THE ASSOCIATION BETWEEN HISTONE MODIFICATIONS AND STEROIDOGENIC GENE REGULATION, THE LEVELS OF THESE HISTONE MARKS WERE FURTHER MEASURED IN STEROIDOGENIC GENE PROMOTER REGIONS BY CHIP. IT WAS FOUND THAT H3K18AC WAS AUGMENTED IN CYP11A1 PROMOTER, AND H3K9AC WAS INCREASED IN HSD3B AFTER PFOS EXPOSURE, WHICH IS PROPOSED TO RESULT IN THE ACTIVATION OF CYP11A1 AND 3BETA-HSD, RESPECTIVELY. TO SUM UP, CHRONIC LOW-LEVEL PFOS EXPOSURE ACTIVATED KEY STEROIDOGENIC GENE EXPRESSION THROUGH ENHANCING HISTONE ACETYLATION (H3K9AC AND H3K18AC), ULTIMATELY STIMULATING STEROID HORMONE BIOSYNTHESIS IN RAT TESTIS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
7  3774 15 INTERACTION OF GONADAL HORMONES, DOPAMINERGIC SYSTEM, AND EPIGENETIC REGULATION IN THE GENERATION OF SEX DIFFERENCES IN SUBSTANCE USE DISORDERS: A SYSTEMATIC REVIEW. SUBSTANCE USE DISORDER (SUD) IS A CHRONIC CONDITION CHARACTERIZED BY PATHOLOGICAL DRUG-TAKING AND SEEKING BEHAVIORS. REMARKABLY DIFFERENT BETWEEN MALES AND FEMALES, SUGGESTING THAT DRUG ADDICTION IS A SEXUALLY DIFFERENTIATED DISORDER. THE NEUROBIOLOGICAL BASES OF SEX DIFFERENCES IN SUD INCLUDE SEX-SPECIFIC REWARD SYSTEM ACTIVATION, INFLUENCED BY INTERACTIONS BETWEEN GONADAL HORMONE LEVEL CHANGES, DOPAMINERGIC REWARD CIRCUITS, AND EPIGENETIC MODIFICATIONS OF KEY REWARD SYSTEM GENES. THIS SYSTEMATIC REVIEW, ADHERING TO PICOS AND PRISMA-P 2015 GUIDELINES, HIGHLIGHTS THE SEX-DEPENDENT ROLES OF ESTROGENS, PROGESTERONE, AND TESTOSTERONE IN SUD. IN PARTICULAR, ESTRADIOL ELEVATES AND PROGESTERONE REDUCES DOPAMINERGIC ACTIVITY IN SUD FEMALES, WHILST TESTOSTERONE AND PROGESTERONE AUGMENT SUD BEHAVIOR IN MALES. FINALLY, SUD IS ASSOCIATED WITH A SEX-SPECIFIC INCREASE IN THE RATE OF OPIOID AND MONOAMINERGIC GENE METHYLATION. THE STUDY REVEALS THE NEED FOR DETAILED RESEARCH ON GONADAL HORMONE LEVELS, DOPAMINERGIC OR REWARD SYSTEM ACTIVITY, AND EPIGENETIC LANDSCAPES IN BOTH SEXES FOR EFFICIENT SUD THERAPY DEVELOPMENT.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8  4095 16 MATERNALLY DERIVED LOW GLUCOCORTICOID MEDIATES ADRENAL DEVELOPMENTAL PROGRAMMING ALTERATION IN OFFSPRING INDUCED BY DEXAMETHASONE. ADVERSE ENVIRONMENTS DURING PREGNANCY CAN INCREASE SUSCEPTIBILITY TO CHRONIC DISEASES IN ADULT OFFSPRING. THE OCCURRENCE AND DEVELOPMENT OF FETAL-ORIGINATED DISEASES WERE ASSOCIATED WITH ADRENAL DEVELOPMENTAL PROGRAMMING AND HOMEOSTASIS ALTERATION IN OFFSPRING. DEXAMETHASONE IS WIDELY USED FOR PRETERM DELIVERY-RELATED PREGNANCY DISEASES, BUT THE INTRAUTERINE PROGRAMMING ALTERATION AND ITS OCCURRENCE MECHANISM OF PRENATAL DEXAMETHASONE EXPOSURE (PDE) ON ADRENAL DEVELOPMENT IN OFFSPRING HAVE NOT BEEN CLARIFIED. IN THIS STUDY, PRENATAL DEXAMETHASONE THERAPY COULD INHIBIT NEONATAL DEVELOPMENT AND CAUSE A LOW EXPOSURE OF MATERNALLY DERIVED GLUCOCORTICOID IN CLINIC. THEN, WE ESTABLISHED A RAT MODEL OF PDE AND OBSERVED A SIMILAR PHENOMENON. FURTHER, THE ADRENAL STEROIDOGENIC FUNCTION WAS CONTINUOUSLY INHIBITED IN THE PDE MALE OFFSPRING RATS, ACCOMPANIED BY THE DECREASED H3K27AC LEVEL OF ADRENAL INSULIN-LIKE GROWTH FACTOR 1 (IGF1) AND ITS EXPRESSION. MOREOVER, CHRONIC STRESS IN PDE ADULT OFFSPRING RATS COULD REVERSE THE CHANGES OF THE ABOVE INDICATORS THROUGH THE HIGH LEVEL OF GLUCOCORTICOID. IN COMBINATION WITH IN VIVO, IN VITRO AND A SERIES OF INTERFERENCE EXPERIMENTS, WE CONFIRMED THAT THE LOW LEVEL OF ENDOGENOUS GLUCOCORTICOIDS INHIBITED THE ADRENAL IGF1 EXPRESSION AND STEROIDOGENIC FUNCTION THROUGH THE GRALPHA/MIR-370-3P/SIRT3 PATHWAY. IN SUMMARY, PDE COULD CONTINUOUSLY INHIBIT THE ADRENAL STEROIDOGENIC FUNCTION IN THE MALE OFFSPRING, WHICH IS ASSOCIATED WITH THE MATERNALLY DERIVED LOW GLUCOCORTICOID-MEDIATED THE ADRENAL DEVELOPMENTAL PROGRAMMING ALTERATION IN OFFSPRING. THIS STUDY PROVIDES A THEORETICAL AND EXPERIMENTAL BASIS FOR EXPLAINING THE ADRENAL DEVELOPMENT ORIGIN OF PDE-INDUCED ADULT CHRONIC DISEASES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
9  1417 18 DIETARY TRENDS AND THE DECLINE IN MALE REPRODUCTIVE HEALTH. OVER THE TWENTIETH CENTURY, MALE REPRODUCTIVE HEALTH HAS SUFFERED A SUBSTANTIAL DECLINE, AS EVIDENCED BY DECREASES IN SPERM COUNTS AND TESTOSTERONE LEVELS AND INCREASES IN REPRODUCTIVE PATHOLOGIES. AT THE SAME TIME, THE PREVALENCE OF CHRONIC DISEASES SUCH AS OBESITY, DIABETES, AND METABOLIC SYNDROME HAS RISEN DRAMATICALLY. METABOLIC AND REPRODUCTIVE HEALTH ARE HIGHLY INTERCONNECTED, SUGGESTING THAT THEIR RESPECTIVE TRENDS ARE INTERTWINED AND, GIVEN THE TIMEFRAME OF SUCH TRENDS, ENVIRONMENTAL AND NOT GENETIC FACTORS ARE MOST LIKELY TO BE THE PRIMARY CAUSES. INDUSTRIALIZATION, WHICH BEGAN IN EUROPE IN THE MID-EIGHTEENTH CENTURY, HAS RESULTED IN PROFOUND CHANGES TO OUR DIET, LIFESTYLE, AND ENVIRONMENT, MANY OF WHICH ARE CAUSAL FACTORS IN THE RISE IN CHRONIC DISEASES. INDUSTRIALIZATION RESULTS IN A NUTRITION TRANSITION FROM AN AGRICULTURAL UNPROCESSED TO A MODERN PROCESSED DIET, INCORPORATING INCREASES IN SUGAR, VEGETABLE OILS, ULTRA-PROCESSED FOODS, LINOLEIC ACID, TRANS-FATS, AND TOTAL ENERGY. THIS DIETARY SHIFT HAS INCURRED NUMEROUS ADVERSE EFFECTS ON METABOLIC AND REPRODUCTIVE HEALTH, CHARACTERIZED BY CHRONIC INFLAMMATION, OXIDATIVE STRESS, AND INSULIN RESISTANCE. MOREOVER, THESE EFFECTS APPEAR TO MULTIPLY ACROSS SUBSEQUENT GENERATIONS VIA EPIGENETIC INHERITANCE. MEN'S FERTILITY IS MARKEDLY AFFECTED BY OBESITY AND DIABETES, WITH AN INCREASE IN TOTAL ENERGY VIA PROCESSED FOOD INTAKE ARGUABLY BEING THE KEY FACTOR DRIVING THE DIABESITY PANDEMIC. IN CONTRAST, WHOLEFOODS RICH IN MICRONUTRIENTS AND PHYTONUTRIENTS SUPPORT MALE FERTILITY AND A HEALTHY BODY WEIGHT. THEREFORE, MEN WANTING TO MAXIMIZE THEIR FERTILITY SHOULD CONSIDER MAKING POSITIVE DIETARY CHANGES, SUCH AS REPLACING PROCESSED FOODS WITH UNPROCESSED FOODS THAT SUPPORT METABOLIC AND REPRODUCTIVE HEALTH.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
10  5878 24 SYNERGISTIC EFFECTS OF HYPERANDROGENEMIA AND OBESOGENIC WESTERN-STYLE DIET ON TRANSCRIPTION AND DNA METHYLATION IN VISCERAL ADIPOSE TISSUE OF NONHUMAN PRIMATES. POLYCYSTIC OVARY SYNDROME (PCOS) IS A MAJOR REPRODUCTIVE DISORDER THAT IS RESPONSIBLE FOR 80% OF ANOVULATORY INFERTILITY AND THAT IS ASSOCIATED WITH HYPERANDROGENEMIA, INCREASED RISK OF OBESITY, AND WHITE ADIPOSE TISSUE (WAT) DYSFUNCTION. WE HAVE PREVIOUSLY DEMONSTRATED THAT THE COMBINATION OF CHRONIC TESTOSTERONE (T) TREATMENT AND AN OBESOGENIC WESTERN-STYLE DIET (WSD) EXERTS SYNERGISTIC FUNCTIONAL EFFECTS ON WAT, LEADING TO INCREASED LIPID ACCUMULATION IN VISCERAL ADIPOCYTES BY AN UNKNOWN MECHANISM. IN THIS STUDY, WE EXAMINED THE WHOLE-GENOME TRANSCRIPTIONAL RESPONSE IN VISCERAL WAT TO T AND WSD, ALONE AND IN COMBINATION. WE OBSERVED A SYNERGISTIC EFFECT OF T AND WSD ON GENE EXPRESSION, RESULTING IN UPREGULATION OF LIPID STORAGE GENES CONCOMITANT WITH ADIPOCYTE HYPERTROPHY. BECAUSE DNA METHYLATION IS KNOWN TO BE ASSOCIATED WITH BODY FAT DISTRIBUTION AND THE ETIOLOGY OF PCOS, WE CONDUCTED WHOLE-GENOME DNA METHYLATION ANALYSIS OF VISCERAL WAT. WHILE ONLY A FRACTION OF DIFFERENTIALLY EXPRESSED GENES ALSO EXHIBITED DIFFERENTIAL DNA METHYLATION, IN SILICO ANALYSIS SHOWED THAT DIFFERENTIALLY METHYLATED REGIONS WERE ENRICHED IN TRANSCRIPTION FACTOR BINDING MOTIFS, SUGGESTING A POTENTIAL GENE REGULATORY ROLE FOR THESE REGIONS. IN SUMMARY, THIS STUDY DEMONSTRATES THAT HYPERANDROGENEMIA ALONE DOES NOT INDUCE GLOBAL TRANSCRIPTIONAL AND EPIGENETIC RESPONSE IN YOUNG FEMALE MACAQUES UNLESS COMBINED WITH AN OBESOGENIC DIET.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
11    86 15 A PATERNAL HYPERCALORIC DIET AFFECTS THE METABOLISM AND FERTILITY OF F1 AND F2 WISTAR RAT GENERATIONS. INCREASED FAT AND CARBOHYDRATE INTAKES BASED ON THE WESTERN DIET ARE IMPORTANT LIFESTYLE MODIFICATIONS THAT LEAD TO HYPERCALORIC INPUTS, OBESITY, AND MALE FERTILITY NEGATIVE EFFECTS. EPIGENETIC TRANSMISSION MAY ALSO PREDISPOSE DESCENDED GENERATIONS TO CHRONIC DISEASES, SUCH AS OBESITY, TYPE 2 DIABETES, BEHAVIORAL, AND REPRODUCTIVE DISORDERS. THE PRESENT STUDY SOUGHT TO EVALUATE THE INFLUENCE OF A HIGH-FAT-HIGH-SUGAR (HFHS) DIET SUPPLIED TO WISTAR RATS FROM 25 TO 90 DAYS OF LIFE ON REPRODUCTIVE AND METABOLIC PARAMETERS IN MALE GENERATIONS F0, F1, AND F2. THE STANDARD GROUP RECEIVED THE NORMOCALORIC - NUVILAB QUIMTIA(R) -3.86 KCAL/KG. THE HYPERCALORIC DIET (HD) GROUP RECEIVED THE HFHS DIET - PRAGSOLUCOES(R) -4.77 KCAL/KG. BODY WEIGHT, ADIPOSITY, F1 AND F2 PREPUBERTAL AGE EVALUATIONS, ORAL GLUCOSE TOLERANCE TEST, INSULIN TOLERANCE TEST, ORGAN WEIGHTS, SPERM COUNT AND MORPHOLOGY ASSESSMENTS, AND HISTOMETRIC TESTICULAR ANALYSES WERE PERFORMED. THE HFHS DIET PROMOTED DYSLIPIDEMIA, HIGHER ADIPOSITY, LOWER RELATIVE ORGAN WEIGHTS, AND HIGHER MEAN KIDNEY WEIGHT, DECREASED MEAN TESTICLE AND PARENCHYMA WEIGHTS AND LOWER HEIGHT OF SEMINIFEROUS EPITHELIUM (HE) FOR THE F0 GENERATION. F1 AND F2 OFFSPRING OF HD GROUP DISPLAYED EARLY PREPREPUBERTAL DEVELOPMENT, ALTHOUGH DID NOT ALTER THE METABOLIC PARAMETERS. DECREASED HE AND TUBULAR TESTICULAR COMPARTMENT VOLUMETRIC DENSITY AND INCREASED INTERTUBULAR TESTICULAR COMPARTMENT VOLUMETRIC DENSITY AND VOLUME IN THE F1 GENERATION OF HD GROUP WERE OBSERVED. ALTERATIONS IN HISTOMETRY OF INTERTUBULAR TESTICULAR COMPARTMENT WERE ALSO NOTED. IT IS CONCLUDED THAT THE HFHS EXPERIMENTAL MODEL ALTERED ONLY PATERNAL METABOLIC PARAMETERS. HOWEVER, REPRODUCTIVE PARAMETERS OF THE THREE GENERATIONS WERE AFFECTED.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
12  5662 17 SEXUAL DIMORPHISM IN GLUCOCORTICOID STRESS RESPONSE. CHRONIC STRESS IS ENCOUNTERED IN OUR EVERYDAY LIFE AND IS THOUGHT TO CONTRIBUTE TO A NUMBER OF DISEASES. MANY OF THESE STRESS-RELATED DISORDERS DISPLAY A SEX BIAS. BECAUSE GLUCOCORTICOID HORMONES ARE THE MAIN BIOLOGICAL MEDIATOR OF CHRONIC STRESS, RESEARCHERS HAVE BEEN INTERESTED IN UNDERSTANDING THE SEXUAL DIMORPHISM IN GLUCOCORTICOID STRESS RESPONSE TO BETTER EXPLAIN THE SEX BIAS IN STRESS-RELATED DISEASES. ALTHOUGH NOT YET DEMONSTRATED FOR GLUCOCORTICOID REGULATION, SEX CHROMOSOMES DO INFLUENCE SEX-SPECIFIC BIOLOGY AS SOON AS CONCEPTION. THEN A TRANSIENT RISE IN TESTOSTERONE START TO SHAPE THE MALE BRAIN DURING THE PRENATAL PERIOD DIFFERENTLY TO THE FEMALE BRAIN. THESE ORGANIZATIONAL EFFECTS ARE COMPLETED JUST BEFORE PUBERTY. THE CEREBRAL REGIONS IMPLICATED IN GLUCOCORTICOID REGULATION AT REST AND AFTER STRESS ARE THEREBY IMPACTED IN A SEX-SPECIFIC MANNER. AFTER PUBERTY, THE HIGH LEVELS OF ALL GONADAL HORMONES WILL INTERACT WITH GLUCOCORTICOID HORMONES IN SPECIFIC CROSSTALK THROUGH THEIR RESPECTIVE NUCLEAR RECEPTORS. IN ADDITION, STRESS OCCURRING EARLY IN LIFE, IN PARTICULAR DURING THE PRENATAL PERIOD AND IN ADOLESCENCE WILL PRIME IN THE LONG-TERM GLUCOCORTICOID STRESS RESPONSE THROUGH EPIGENETIC MECHANISMS, AGAIN IN A SEX-SPECIFIC MANNER. ALTOGETHER, VARIOUS MOLECULAR MECHANISMS EXPLAIN SEX-SPECIFIC GLUCOCORTICOID STRESS RESPONSES THAT DO NOT EXCLUDE IMPORTANT GENDER EFFECTS IN HUMANS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
13  5198 19 PRENATAL HIGH ESTRADIOL EXPOSURE INDUCES SEX-SPECIFIC AND DIETARILY REVERSIBLE INSULIN RESISTANCE THROUGH DECREASED HYPOTHALAMIC INSR. AN ADVERSE INTRAUTERINE ENVIRONMENT MAY INDUCE ADULT DISEASE IN OFFSPRING, BUT THE MECHANISMS ARE NOT WELL UNDERSTOOD. IT IS REPORTED THAT FRESH EMBRYO TRANSFER (ET) IN ASSISTED REPRODUCTIVE TECHNOLOGY LEADS TO HIGH MATERNAL ESTRADIOL (E2), AND PRENATAL HIGH E2 EXPOSURE INCREASES THE RISK OF ORGAN DISORDERS IN LATER LIFE. WE FOUND THAT MALE NEWBORNS AND CHILDREN OF FRESH ET SHOWED ELEVATED FASTING INSULIN AND HOMEOSTASIS MODEL OF ASSESSMENT FOR INSULIN RESISTANCE INDEX (HOMA-IR) SCORES. MALE MICE WITH HIGH PRENATAL ESTRADIOL EXPOSURE (HE) GREW HEAVIER THAN CONTROL MICE AND DEVELOPED INSULIN RESISTANCE; THEY ALSO SHOWED INCREASED FOOD INTAKE, WITH INCREASED OREXIGENIC HYPOTHALAMIC NEUROPEPTIDE Y (NPY) EXPRESSION. THE HYPOTHALAMIC INSULIN RECEPTOR (INSR) WAS DECREASED IN MALE HE MICE, ASSOCIATED WITH ELEVATED PROMOTER METHYLATION. CHRONIC FOOD RESTRICTION (FR) IN HE MICE REVERSED INSULIN RESISTANCE AND RESCUED HYPOTHALAMIC INSR EXPRESSION BY CORRECTING THE ELEVATED INSR PROMOTER METHYLATION. OUR FINDINGS SUGGEST THAT PRENATAL EXPOSURE TO HIGH E2 MAY INDUCE SEX-SPECIFIC METABOLIC DISORDERS IN LATER LIFE THROUGH EPIGENETIC PROGRAMMING OF HYPOTHALAMIC INSR PROMOTER, AND DIETARY INTERVENTION MAY REVERSE INSULIN RESISTANCE BY REMODELING ITS METHYLATION PATTERN.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
14  3812 21 INTRAUTERINE ENDOGENOUS HIGH GLUCOCORTICOIDS PROGRAM OVARIAN DYSFUNCTION IN FEMALE OFFSPRING SECONDARY TO PRENATAL CAFFEINE EXPOSURE. OVARIAN DYSFUNCTION HAS AN INTRAUTERINE ORIGIN, AND PRENATAL CAFFEINE EXPOSURE (PCE) COULD LEAD TO ABNORMAL FOLLICLE COUNTS IN OFFSPRING AFTER BIRTH. HOWEVER, THE EFFECT OF PCE ON OFFSPRING OVARIAN FUNCTION AND ITS MECHANISM OF INTRAUTERINE PROGRAMMING HAVE NOT BEEN REPORTED THUS FAR. IN THIS STUDY, PREGNANT WISTAR RATS WERE INTRAGASTRICALLY ADMINISTERED CAFFEINE (30 AND 120 MG/KG.D) AT GESTATIONAL DAYS 9-20 (GD9-20). CERTAIN TESTS WERE PERFORMED ON THE BLOOD, OVARIES AND HYPOTHALAMUS OF FEMALE OFFSPRING AT DIFFERENT TIME POINTS. PCE FEMALE OFFSPRING HAD OVARIAN DYSFUNCTION IN ADULTHOOD COMPARED WITH THE CONTROL. FURTHER RESULTS SHOWED THAT IN UTERO OVARIAN MORPHOLOGICAL DEVELOPMENT AND ESTRADIOL SYNTHESIS WERE INHIBITED BUT RAPIDLY INCREASED DURING PUBERTY IN THE PCE GROUP. THE HISTONE 3 LYSINE 27 ACETYLATION (H3K27AC) LEVEL OF THE INSULIN-LIKE GROWTH FACTOR 1 (IGF1) PROMOTER REGION AND ITS EXPRESSION WERE DECREASED IN THE OVARY, WHICH WAS DUE TO EXPOSURE TO HIGH LEVELS OF FETAL BLOOD CORTICOSTERONE, AND THE H3K27AC LEVEL OF IGF1 AND ITS EXPRESSION SHIFTED TO INCREASE AFTER BIRTH WITH A DECREASE IN SERUM CORTICOSTERONE LEVELS. CHRONIC STRESS LED TO INCREASED SERUM CORTICOSTERONE LEVELS IN ADULT OFFSPRING, WHEREAS OVARIAN MORPHOLOGICAL DEVELOPMENT, THE H3K27AC LEVEL OF IGF1 AND ITS EXPRESSION, AND ESTRADIOL SYNTHESIS WERE SIGNIFICANTLY INHIBITED. MOREOVER, THE ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-OVARIAN (HPO) AXIS WAS INCREASED IN THE EARLY POSTNATAL PERIOD OF PCE OFFSPRING, AND CHRONIC STRESS REVERSED THESE CHANGES. IN THE KGN CELL LINE, IT WAS FOUND THAT CORTISOL COULD PROMOTE THE TRANSLOCATION OF THE GLUCOCORTICOID RECEPTOR (GR) INTO THE NUCLEUS AND UPREGULATE HISTONE DEACETYLASE 10 (HDAC10) TO INHIBIT THE H3K27AC LEVEL OF IGF1 AND ITS EXPRESSION AND ESTRADIOL SYNTHESIS. IN SUMMARY, PCE IS ASSOCIATED WITH OVARIAN DYSFUNCTION IN FEMALE ADULT OFFSPRING, AND THE POTENTIAL MECHANISM IS RELATED TO INTRAUTERINE HIGH GLUCOCORTICOID EXPOSURE BY ACTIVATING THE GR AND RECRUITING HDAC10 TO AFFECT OVARIAN GLUCOCORTICOID-IGF1 AXIS PROGRAMMING AND TO INHIBIT ESTRADIOL SYNTHESIS.	2021	
                                                                                   
15  6601 17 TWO INTRAUTERINE PROGRAMMING MECHANISMS OF ADULT HYPERCHOLESTEROLEMIA INDUCED BY PRENATAL NICOTINE EXPOSURE IN MALE OFFSPRING RATS. EPIDEMIOLOGIC STUDIES SHOWED THAT LOW BIRTH WEIGHT IS ASSOCIATED WITH HIGH CHOLESTEROL AND AN INCREASED RISK OF CARDIOVASCULAR DISEASES IN ADULTHOOD. THIS STUDY AIMED TO ELUCIDATE THE INTRAUTERINE PROGRAMMING MECHANISMS OF ADULT HYPERCHOLESTEROLEMIA. THE RESULTS SHOWED THAT PRENATAL NICOTINE EXPOSURE (PNE) CAUSED INTRAUTERINE GROWTH RETARDATION AND HYPERCHOLESTEROLEMIA IN MALE ADULT OFFSPRING RATS. HEPATIC CHOLESTEROL SYNTHESIS AND OUTPUT WERE DECEASED IN UTERO BUT INCREASED IN ADULTS; HEPATIC REVERSE CHOLESTEROL TRANSPORT (RCT) PERSISTENTLY DECEASED BEFORE AND AFTER BIRTH. MEANWHILE, PNE ELEVATED SERUM CORTICOSTERONE LEVEL AND DECREASED HEPATIC IGF1 PATHWAY ACTIVITY IN MALE FETUSES, WHEREAS CONVERSE CHANGES WERE OBSERVED IN MALE ADULTS. THE CHRONIC STRESS MODEL AND CORTISOL-TREATED HEPG2 CELLS VERIFIED THAT EXCESSIVE GLUCOCORTICOID (GC)-INDUCED GC-IGF1 AXIS PROGRAMMING ENHANCED HEPATIC CHOLESTEROL SYNTHESIS AND OUTPUT. IN ADDITION, PNE DECREASED THE EXPRESSION OF SPECIFIC PROTEIN 1 AND P300 ENRICHMENT AND H3K27 ACETYLATION AT THE PROMOTER REGION OF GENES RESPONSIBLE FOR RCT BOTH IN FETAL AND ADULT, MALE LIVERS AND REDUCED EXPRESSION OF THOSE GENES, SIMILAR ALTERATIONS WERE ALSO CONFIRMED IN CORTISOL-TREATED HEPG2 CELLS, SUGGESTING THAT EXCESSIVE GC-RELATED PROGRAMMING INDUCED CONTINUOUS RCT REDUCTION BY EPIGENETIC MODIFICATION. TAKEN TOGETHER, THE "2-PROGRAMMING" APPROACH DISCUSSED ABOVE MAY ULTIMATELY CONTRIBUTE TO THE DEVELOPMENT OF HYPERCHOLESTEROLEMIA IN MALE ADULT OFFSPRING.-ZHOU, J., ZHU, C., LUO, H., SHEN, L., GONG, J., WU, Y., MAGDALOU, J., CHEN, L., GUO, Y., WANG, H. TWO INTRAUTERINE PROGRAMMING MECHANISMS OF ADULT HYPERCHOLESTEROLEMIA INDUCED BY PRENATAL NICOTINE EXPOSURE IN MALE OFFSPRING RATS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
16  5253 18 PROGRAMMING CHANGES OF HIPPOCAMPAL MIR-134-5P/SOX2 SIGNAL MEDIATE THE SUSCEPTIBILITY TO DEPRESSION IN PRENATAL DEXAMETHASONE-EXPOSED FEMALE OFFSPRING. DEPRESSION IS A NEUROPSYCHIATRIC DISORDER AND HAS INTRAUTERINE DEVELOPMENTAL ORIGINS. THIS STUDY AIMED TO CONFIRM THE DEPRESSION SUSCEPTIBILITY IN OFFSPRING RATS INDUCED BY PRENATAL DEXAMETHASONE EXPOSURE (PDE) AND TO FURTHER EXPLORE THE INTRAUTERINE PROGRAMMING MECHANISM. WISTAR RATS WERE INJECTED WITH DEXAMETHASONE (0.2 MG/KG.D) SUBCUTANEOUSLY DURING THE GESTATIONAL DAYS 9-20 AND PART OF THE OFFSPRING WAS GIVEN CHRONIC STRESS AT POSTNATAL WEEKS 10-12. BEHAVIORAL RESULTS SHOWED THAT THE ADULT PDE FEMALE OFFSPRING WAS SUSCEPTIBLE TO DEPRESSION, ACCOMPANIED BY INCREASED HIPPOCAMPAL MIR-134-5P EXPRESSION AND DECREASED SEX-DETERMINING REGION Y-BOX 2 (SOX2) EXPRESSION, AS WELL AS DISORDERS OF NEURAL PROGENITOR CELLS PROLIFERATION AND HIPPOCAMPAL NEUROGENESIS. THE PDE FEMALE FETAL RATS PRESENTED CONSISTENT CHANGES WITH THE ADULT OFFSPRING, ACCOMPANIED BY THE UPREGULATION OF GLUCOCORTICOID RECEPTOR (GR) EXPRESSION AND DECREASED SIRTUIN 1 (SIRT1) EXPRESSION. WE FURTHER FOUND THAT THE H3K9AC LEVEL OF THE MIR-134-5P PROMOTER WAS SIGNIFICANTLY INCREASED IN THE PDE FETAL HIPPOCAMPUS, AS WELL AS IN ADULT OFFSPRING BEFORE AND AFTER CHRONIC STRESS. IN VITRO, THE CHANGES OF GR/SIRT1/MIR-134-5P/SOX2 SIGNAL BY DEXAMETHASONE WERE CONSISTENT WITH IN VIVO EXPERIMENTS, WHICH COULD BE REVERSED BY GR RECEPTOR ANTAGONIST, SIRT1 AGONIST, AND MIR-134-5P INHIBITOR. THIS STUDY CONFIRMED THAT PDE LED TO AN INCREASED EXPRESSION LEVEL AS WELL AS H3K9AC LEVEL OF MIR-134-5P BY ACTIVATING THE GR/SIRT1 PATHWAY IN THE FETAL HIPPOCAMPUS AND THEN INHIBITED THE SOX2 EXPRESSION. THE PROGRAMMING EFFECT MEDIATED BY THE ABNORMAL EPIGENETIC MODIFICATION COULD LAST FROM INTRAUTERINE TO ADULTHOOD, WHICH CONSTITUTES THE INTRAUTERINE PROGRAMMING MECHANISM LEADING TO HIPPOCAMPAL NEUROGENESIS DISORDERS AND DEPRESSION SUSCEPTIBILITY IN FEMALE OFFSPRING. INTRAUTERINE PROGRAMMING MECHANISM FOR THE INCREASED DEPRESSIVE SUSCEPTIBILITY IN ADULT FEMALE OFFSPRING BY PRENATAL DEXAMETHASONE EXPOSURE (PDE). GR, GLUCOCORTICOID RECEPTOR; SIRT1, SIRTUIN 1; SOX2, SEX-DETERMINING REGION Y-BOX 2; NPCS, NEUROPROGENITOR CELLS; H3K9AC, HISTONE 3 LYSINE 9 ACETYLATION; GRE, GLUCOCORTICOID RESPONSE ELEMENT.	2022	

17  4886 21 OVERWEIGHT AND OBESITY BEFORE, DURING AND AFTER PREGNANCY: PART 1: PATHOPHYSIOLOGY, MOLECULAR BIOLOGY AND EPIGENETIC CONSEQUENCES. OVERWEIGHT AND OBESITY BEFORE CONCEPTION AS WELL AS EXCESSIVE WEIGHT GAIN DURING PREGNANCY ARE ASSOCIATED WITH ENDOCRINOLOGICAL CHANGES OF MOTHER AND FETUS. INSULIN RESISTANCE PHYSIOLOGICALLY INCREASES DURING PREGNANCY, ADDITIONAL OBESITY FURTHER INCREASES INSULIN RESISTANCE. IN COMBINATION WITH REDUCED INSULIN SECRETION THIS LEADS TO GESTATIONAL DIABETES WHICH MAY DEVELOP INTO TYPE-2-DIABETES. THE ADIPOSE TISSUE PRODUCES TNF-ALPHA, INTERLEUKINS AND LEPTIN AND UPREGULATES THESE ADIPOKINES. INSULIN RESISTANCE AND OBESITY INDUCE INFLAMMATORY PROCESSES AND VASCULAR DYSFUNCTION, WHICH EXPLAINS THE INCREASED RATE OF PREGNANCY-RELATED HYPERTENSION AND PRE-ECLAMPSIA IN OBESE PREGNANT WOMEN. BETWEEN 14 AND 28 GESTATIONAL WEEKS, THE FETAL ADIPOSE TISSUE IS GENERATED AND THE NUMBER OF FAT LOBULES IS DETERMINED. THEREAFTER, AN INCREASE IN ADIPOSE TISSUE IS ARRANGED BY AN ENLARGEMENT OF THE LOBULES (HYPERTROPHY), OR EVEN AN INCREASE IN THE NUMBER OF FAT CELLS (HYPERPLASIA). HUMAN AND ANIMAL STUDIES HAVE SHOWN THAT MATERNAL OBESITY "PROGRAMMES" THE OFFSPRING FOR FURTHER OBESITY AND CHRONIC DISEASE. PREGNANT WOMEN, MIDWIVES, PHYSICIANS AND HEALTH CARE POLITICIANS SHOULD BE BETTER INFORMED ABOUT PREVENTION, PATHOPHYSIOLOGICAL MECHANISMS, AND THE BURDEN FOR SOCIETY CAUSED BY OBESITY BEFORE, DURING AND AFTER PREGNANCY.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
18  5104 18 POLYCYSTIC OVARIAN SYNDROME. WOMEN WITH PCOS PRESENT WITH SIGNS OF CHRONIC ANOVULATION, HYPERANDROGENISM, AND METABOLIC ABNORMALITIES. THE NIH RECENTLY EMBRACED THE ROTTERDAM CRITERIA TO BROADLY IDENTIFY ALL THE PHENOTYPES OF PCOS. WOMEN WITH PCOS ARE OFTEN OBESE WITH INSULIN RESISTANCE AND HENCE HAVE AN INCREASED SUSCEPTIBILITY TO GLUCOSE INTOLERANCE AND TYPE 2 DIABETES. FUTURE RESEARCH SHOULD FOCUS ON THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL DETERMINANTS OF PCOS TO DEVELOP NEW THERAPIES TO ADDRESS THE PREVENTION OF THIS DISORDER AND ITS LONG-TERM COMPLICATIONS.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19  4939 17 PATERNAL NICOTINE EXPOSURE IN RATS PRODUCES LONG-LASTING NEUROBEHAVIORAL EFFECTS IN THE OFFSPRING. STUDIES OF INTERGENERATIONAL EFFECTS OF PARENTAL CHEMICAL EXPOSURE HAVE PRINCIPALLY FOCUSED ON MATERNAL EXPOSURE, PARTICULARLY FOR STUDIES OF ADVERSE NEUROBEHAVIORAL CONSEQUENCES ON THE OFFSPRING. MATERNAL NICOTINE EXPOSURE HAS LONG BEEN KNOWN TO CAUSE ADVERSE NEUROBEHAVIORAL EFFECTS ON THE OFFSPRING. HOWEVER, PATERNAL TOXICANT EXPOSURE HAS ALSO BEEN FOUND TO CAUSE NEUROBEHAVIORAL TOXICITY IN THEIR OFFSPRING. RECENT WORK SUGGESTS THAT PATERNAL NICOTINE EXPOSURE CAN HAVE EPIGENETIC EFFECTS, ALTHOUGH IT REMAINS UNCLEAR WHETHER SUCH CHANGES LEAD TO NEUROBEHAVIORAL EFFECTS. IN THE CURRENT STUDY, WE INVESTIGATED THE EFFECTS OF PATERNAL NICOTINE EXPOSURE ON NEUROBEHAVIORAL DEVELOPMENT OF THEIR OFFSPRING. MALE SPRAGUE-DAWLEY RATS WERE EXPOSED TO 0 OR 2 MG/KG/DAY NICOTINE (SC) FOR 56 CONSECUTIVE DAYS WITH TWO CONSECUTIVE 2ML4 OSMOTIC MINIPUMPS. FOLLOWING TREATMENT, THESE MALES WERE MATED WITH DRUG-NAIVE FEMALE RATS. OFFSPRING OF BOTH SEXES WERE TESTED IN A BEHAVIORAL BATTERY TO ASSESS LOCOMOTION, EMOTIONAL FUNCTION AND COGNITION. PATERNAL NICOTINE EXPOSURE DID NOT IMPACT OFFSPRING VIABILITY, HEALTH OR GROWTH. HOWEVER, BEHAVIORAL FUNCTION OF THE OFFSPRING WAS SIGNIFICANTLY ALTERED BY PATERNAL NICOTINE EXPOSURE. MALE OFFSPRING WITH PATERNAL NICOTINE EXPOSURE EXHIBITED LOCOMOTOR HYPERACTIVITY IN THE FIGURE-8 APPARATUS WHEN TESTED DURING ADOLESCENCE. WHEN RETESTED IN ADULTHOOD AND REGARDLESS OF SEX, OFFSPRING OF THE NICOTINE EXPOSED FATHER SHOWED SIGNIFICANTLY REDUCED HABITUATION OF LOCOMOTOR ACTIVITY OVER THE COURSE OF THE SESSION. COMPARED TO CONTROLS, FEMALE OFFSPRING OF NICOTINE-EXPOSED FATHERS SHOWED SIGNIFICANTLY REDUCED RESPONSE LATENCY IN THE RADIAL ARM MAZE TEST. IN ADDITION TO LOCOMOTOR HYPERACTIVITY, THE OFFSPRING OF NICOTINE-EXPOSED FATHERS ALSO SHOWED SIGNIFICANTLY DIMINISHED HABITUATION IN THE NOVEL OBJECT RECOGNITION TEST. THESE RESULTS INDICATE THAT CHRONIC PATERNAL NICOTINE EXPOSURE CAN IMPACT THE BEHAVIOR OF OFFSPRING, PRODUCING LOCOMOTOR HYPERACTIVITY AND IMPAIRED HABITUATION.	2019	
                                                                                                                                                                                                               
20  3750 21 INSULIN RESISTANCE IN POLYCYSTIC OVARY SYNDROME ACROSS VARIOUS TISSUES: AN UPDATED REVIEW OF PATHOGENESIS, EVALUATION, AND TREATMENT. POLYCYSTIC OVARY SYNDROME (PCOS) IS A COMMON ENDOCRINE DISORDER CHARACTERIZED BY CHRONIC OVULATION DYSFUNCTION AND OVERABUNDANCE OF ANDROGENS; IT AFFECTS 6-20% OF WOMEN OF REPRODUCTIVE AGE. PCOS INVOLVES VARIOUS PATHOPHYSIOLOGICAL FACTORS, AND AFFECTED WOMEN USUALLY HAVE SIGNIFICANT INSULIN RESISTANCE (IR), WHICH IS A MAJOR CAUSE OF PCOS. IR AND COMPENSATORY HYPERINSULINAEMIA HAVE DIFFERING PATHOGENESES IN VARIOUS TISSUES, AND IR VARIES AMONG DIFFERENT PCOS PHENOTYPES. GENETIC AND EPIGENETIC CHANGES, HYPERANDROGENAEMIA, AND OBESITY AGGRAVATE IR. INSULIN SENSITIZATION DRUGS ARE A NEW TREATMENT MODALITY FOR PCOS. WE SEARCHED PUBMED, GOOGLE SCHOLAR, ELSEVIER, AND UPTODATE DATABASES IN THIS REVIEW, AND FOCUSED ON THE PATHOGENESIS OF IR IN WOMEN WITH PCOS AND THE PATHOPHYSIOLOGY OF IR IN VARIOUS TISSUES. IN ADDITION, THE REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF THE CURRENT PROGRESS IN THE EFFICACY OF INSULIN SENSITIZATION THERAPY IN THE MANAGEMENT OF PCOS, PROVIDING THE LATEST EVIDENCE FOR THE CLINICAL TREATMENT OF WOMEN WITH PCOS AND IR.	2023