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[PMID]: 29345153
[Au] Autor:Ornoy A; Koren G
[Ad] Address:a Laboratory of Teratology, Department of Medical Neurobiology , Hebrew University Hadassah Medical School , Jerusalem , Israel.
[Ti] Title:Selective serotonin reuptake inhibitor use in pregnant women; pharmacogenetics, drug-drug interactions and adverse effects.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):247-259, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:INTRODUCTION: Possible negative effects of selective serotonin reuptake inhibitors (SSRIs) in pregnancy relate to congenital anomalies, negative perinatal events and neurodevelopmental outcome. Many studies are confounded by the underlying maternal disease and by pharmacogenetic and pharmacokinetic differences of these drugs. Areas covered: The possible interactions of SSRIs and serotonin and norepinephrine reuptake inhibitors with other drugs and the known effects of SSRIs on congenital anomalies, perinatal and neurodevelopmental outcome. Expert opinion: SSRIs should be given with caution when combined with other drugs that are metabolized by cytochrome P450 enzymes. SSRIs apparently increase the rate of severe cardiac malformations, induce neonatal adaptation problems in up to 30% of the offspring, increase the rate of persistent pulmonary hypertension of the newborn and possibly slightly increase the rate of prematurity and low birth weight. Most neurodevelopmental follow up studies did not find significant cognitive impairments except some transient gross motor delay, slight impairment of language abilities and possibly behavioral changes. The literature on the possible association of SSRIs with autism spectrum disorder is inconsistent; if an association exists, it is apparently throughout pregnancy. The risk associated with treatment discontinuation seems to outweigh the risk of treatment, as severe maternal depression may negatively affect the child's development. If needed, treatment should continue in pregnancy with the minimal effective dose.
[Mh] MeSH terms primary: Depression/drug therapy
Pregnancy Complications/drug therapy
Serotonin Uptake Inhibitors/administration & dosage
[Mh] MeSH terms secundary: Animals
Drug Interactions
Female
Humans
Infant, Newborn
Pharmacogenetics
Pregnancy
Prenatal Exposure Delayed Effects/epidemiology
Serotonin Uptake Inhibitors/adverse effects
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:0 (Serotonin Uptake Inhibitors)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180119
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1430139

  2 / 25081 MEDLINE  
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[PMID]: 28454694
[Au] Autor:Jawerbaum A; White V
[Ad] Address:Laboratory of Reproduction and Metabolism, Center for Pharmacological and Botanical Studies, CEFyBO-CONICET, School of Medicine, University of Buenos Aires, Argentina. Electronic address: a.jawerbaum@gmail.com.
[Ti] Title:Review on intrauterine programming: Consequences in rodent models of mild diabetes and mild fat overfeeding are not mild.
[So] Source:Placenta;52:21-32, 2017 Apr.
[Is] ISSN:1532-3102
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:An adverse intrauterine programming occurs in diabetes and obesity as the consequence of an adverse maternal environment that affects the appropriate fetoplacental development and growth. Experimental models of diabetes and fat overfeeding have provided relevant tools to address putative mechanisms of the adverse intrauterine programming. The current knowledge far extends from the original thoughts of the resulting intrauterine programming of metabolic and cardiovascular diseases to a full range of alterations that affect multiple tissues, organs, and systems that will compromise the long-life health of the offspring. This review examines the postnatal effects of rodent models of mild diabetes and fat overfeeding, identifying the multiple organ derangements in the offspring resulting from mild maternal adverse conditions. In addition, the comparison of experimental models of severe diabetes and fat overfeeding and the crucial role of the placenta are discussed, providing an update of the actual scenario of the putative mechanisms and adverse consequences of maternal metabolic derangements.
[Mh] MeSH terms primary: Diabetes Mellitus/metabolism
Fetal Development/physiology
Placenta/metabolism
Prenatal Exposure Delayed Effects/metabolism
[Mh] MeSH terms secundary: Animals
Diabetes Mellitus/pathology
Disease Models, Animal
Female
Placenta/pathology
Pregnancy
Prenatal Exposure Delayed Effects/pathology
Rodentia
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[Js] Journal subset:IM
[Da] Date of entry for processing:170430
[St] Status:MEDLINE

  3 / 25081 MEDLINE  
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[PMID]: 29309796
[Au] Autor:Fueta Y; Sekino Y; Yoshida S; Kanda Y; Ueno S
[Ad] Address:Department of Environmental Management and Control, School of Health Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. Electronic address: yukiko@med.uoeh-u.ac.jp.
[Ti] Title:Prenatal exposure to valproic acid alters the development of excitability in the postnatal rat hippocampus.
[So] Source:Neurotoxicology;65:1-8, 2018 Jan 05.
[Is] ISSN:1872-9711
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Prenatal valproic acid (VPA) exposure is a well-known animal model of autism spectrum disorder (ASD) that produces alterations in embryonic and adult neurogenesis as well as adolescent/adulthood neurobehavioral phenotypes. However, the effects of prenatal VPA exposure on neural network excitability, especially during the synaptogenic period around eye opening, are not fully understood. In this study, we orally administered VPA (300 mg/kg) to pregnant Wistar rats on gestation day 15 and subsequently performed field potential recording in the CA1 area of hippocampal slices obtained from control (saline-exposed) and VPA-exposed rat pups between postnatal day (PND) 13 and PND18. In control slices, we observed an abrupt enhancement of stimulation-dependent responses including population spike (PS) amplitudes and field excitatory postsynaptic potential (fEPSP) slopes at PND16, which coincided with the average day of eye opening. In contrast, VPA-exposed pups exhibited delayed eye opening (PND17) and gradual rather than abrupt increases in PS amplitudes and fEPSP slopes over the duration of the synaptogenic period. We next investigated the involvement of ambient GABA (γ-aminobutyric acid) in PS generation using bicuculline methiodide (BMI), a GABA type A (GABA ) receptor antagonist. In control slices, BMI enhanced PS amplitudes during PND14-15 (before eye opening) and had little effect thereafter during PND16-17; a subsequent regression model analysis of BMI ratios (the ratio of PS amplitudes in the presence and absence of BMI) indicated a possible developmental change between these periods. In contrast, almost identical regression models were obtained for BMI ratios during PND14-15 and PND16-17 in the VPA-exposed group, indicating the absence of a developmental change. Our results suggest that prenatal VPA exposure accelerates the development of hippocampal excitability before eye opening. Moreover, our experimental model can be used as a novel approach for the evaluation of developmental neurotoxicity.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher

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[PMID]: 28743040
[Au] Autor:Furlong MA; Herring A; Buckley JP; Goldman BD; Daniels JL; Engel LS; Wolff MS; Chen J; Wetmur J; Barr DB; Engel SM
[Ad] Address:Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, United States. Electronic address: mfurlong@email.arizona.edu.
[Ti] Title:Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes.
[So] Source:Environ Res;158:737-747, 2017 10.
[Is] ISSN:1096-0953
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6-9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (ß^ - 0.13, 95% CI - 0.26, 0.00) but positively associated with Executive Functioning factor scores (ß^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (ß^ - 0.17, 95% CI - 0.33, - 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision.
[Mh] MeSH terms primary: Child Behavior/drug effects
Child Development/drug effects
Environmental Pollutants/toxicity
Executive Function/drug effects
Intelligence/drug effects
Organophosphorus Compounds/toxicity
Prenatal Exposure Delayed Effects/epidemiology
[Mh] MeSH terms secundary: Adolescent
Adult
Child
Female
Humans
Intelligence Tests
Longitudinal Studies
Male
Maternal Exposure
New York City/epidemiology
Pesticides/toxicity
Pregnancy
Prenatal Exposure Delayed Effects/chemically induced
Young Adult
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Name of substance:0 (Environmental Pollutants); 0 (Organophosphorus Compounds); 0 (Pesticides)
[Em] Entry month:1708
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[Js] Journal subset:IM
[Da] Date of entry for processing:170726
[St] Status:MEDLINE

  5 / 25081 MEDLINE  
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[PMID]: 29428599
[Au] Autor:Bukhari SHF; Clark OE; Williamson LL
[Ad] Address:Psychology Department, Williams College, Williamstown, MA 01267, United States.
[Ti] Title:Maternal high fructose diet and neonatal immune challenge alter offspring anxiety-like behavior and inflammation across the lifespan.
[So] Source:Life Sci;197:114-121, 2018 Mar 15.
[Is] ISSN:1879-0631
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:AIMS: This study examined the interaction between maternal high fructose diet and neonatal inflammation in neonates (P7), juveniles (P26-34) and adults on measures of anxiety-like behavior and cognition. The study aimed to assess the potential synergistic effects of these two forms of early-life inflammation. MAIN METHODS: We fed Sprague-Dawley dams with high fructose (60%) diet or normal chow. Each litter was treated with either saline or lipopolysaccharide (LPS) on postnatal day (P)3 and P5 and two pups were tested for USVs after maternal separation on P7. Post-weaning, juveniles were tested on the elevated zero maze (EZM) and in a context-object discrimination (COD) task prior to tissue harvest. Adults were tested on the EZM and the COD task as well. Immunohistochemistry and ELISA were used to assess molecular and cellular changes in the offspring. KEY FINDINGS: This study demonstrates that maternal diet and neonatal inflammation altered peripheral inflammation in neonates, altered anxiety-like behavior in juveniles, and altered anxiety-like behavior in adulthood. Maternal diet and sex increased juvenile peripheral inflammation and altered memory on the context-discrimination task. SIGNIFICANCE: Maternal diet has a profound impact on fetal and neonatal development, especially as obesity rates are on the rise worldwide. Together, these findings reveal enduring effects of maternal diet on offspring, support the findings on the effects of neonatal inflammation on anxiety-like behaviors in later-life periods, and add to the complex relationship between gestational and neonatal inflammation and anxiety.
[Mh] MeSH terms primary: Anxiety
Behavior, Animal/drug effects
Dietary Carbohydrates/adverse effects
Fructose/adverse effects
Prenatal Exposure Delayed Effects
[Mh] MeSH terms secundary: Animals
Anxiety/chemically induced
Anxiety/physiopathology
Dietary Carbohydrates/pharmacology
Female
Fructose/pharmacology
Inflammation/chemically induced
Inflammation/pathology
Inflammation/physiopathology
Lipopolysaccharides/toxicity
Memory/drug effects
Pregnancy
Prenatal Exposure Delayed Effects/chemically induced
Prenatal Exposure Delayed Effects/pathology
Prenatal Exposure Delayed Effects/physiopathology
Rats
Rats, Sprague-Dawley
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Dietary Carbohydrates); 0 (Lipopolysaccharides); 30237-26-4 (Fructose)
[Em] Entry month:1803
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[Js] Journal subset:IM
[Da] Date of entry for processing:180212
[St] Status:MEDLINE

  6 / 25081 MEDLINE  
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[PMID]: 29357379
[Au] Autor:Darwiche W; Gay-Quéheillard J; Delanaud S; El Khayat El Sabbouri H; Khachfe H; Joumaa W; Bach V; Ramadan W
[Ad] Address:PériTox, Périnatalité & Risques Toxiques, UMR-I 01 INERIS, Amiens, France.
[Ti] Title:Impact of chronic exposure to the pesticide chlorpyrifos on respiratory parameters and sleep apnea in juvenile and adult rats.
[So] Source:PLoS One;13(1):e0191237, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The widely used organophosphorus pesticide chlorpyrifos (CPF) is often detected in food. CPF inhibits acetylcholinesterase and can modify muscle contractility and respiratory patterns. We studied the effects of chronic exposure to CPF on respiratory parameters and diaphragm contractility in 21- and 60-days old rats. Pregnant rats were exposed to oral CPF (1 or 5 mg/ kg /day: CPF-1 or CPF-5 groups vs vehicle: controls) from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle) thereafter. Two developmental time points were studied: weaning (day 21) and adulthood (day 60). Whole-body plethysmography was used to score breathing patterns and apnea index during sleep. Then, diaphragm strips were dissected for the assessment of contractility and acetylcholinesterase activity. Results showed that the sleep apnea index was higher in CPF-exposed rats than in controls. In adult rats, the expiratory time and tidal volume were higher in CPF-exposed animals than in controls. At both ages, the diaphragm's amplitude of contraction and fatigability index were higher in the CPF-5 group, due to lower acetylcholinesterase activity. We conclude that chronic exposure to CPF is associated with higher sleep apnea index and diaphragm contractility, and modifies respiratory patterns in sleeping juvenile and adult rats.
[Mh] MeSH terms primary: Chlorpyrifos/toxicity
Pesticides/toxicity
Respiration/drug effects
Sleep Apnea Syndromes/chemically induced
[Mh] MeSH terms secundary: Acetylcholinesterase/metabolism
Animals
Chlorpyrifos/administration & dosage
Cholinesterase Inhibitors/administration & dosage
Cholinesterase Inhibitors/toxicity
Diaphragm/drug effects
Diaphragm/physiopathology
Female
Male
Muscle Contraction/drug effects
Plethysmography, Whole Body
Pregnancy
Prenatal Exposure Delayed Effects/physiopathology
Rats
Sleep Apnea Syndromes/physiopathology
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Cholinesterase Inhibitors); 0 (Pesticides); EC 3.1.1.7 (Acetylcholinesterase); JCS58I644W (Chlorpyrifos)
[Em] Entry month:1802
[Cu] Class update date: 180226
[Lr] Last revision date:180226
[Js] Journal subset:IM
[Da] Date of entry for processing:180123
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191237

  7 / 25081 MEDLINE  
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[PMID]: 29352277
[Au] Autor:Villain H; Benkahoul A; Birmes P; Ferry B; Roullet P
[Ad] Address:Centre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, Toulouse, France.
[Ti] Title:Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment.
[So] Source:PLoS One;13(1):e0191563, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a ß-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the "city-like" test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans.
[Mh] MeSH terms primary: Adrenergic beta-Antagonists/pharmacology
Memory Consolidation/drug effects
Memory Consolidation/physiology
Propranolol/pharmacology
Stress Disorders, Post-Traumatic/drug therapy
Stress Disorders, Post-Traumatic/psychology
[Mh] MeSH terms secundary: Animals
Conditioning, Classical
Corticosterone/blood
Disease Models, Animal
Fear/psychology
Female
Humans
Mice
Pregnancy
Prenatal Exposure Delayed Effects/drug therapy
Prenatal Exposure Delayed Effects/psychology
Stress Disorders, Post-Traumatic/blood
Stress, Physiological
Stress, Psychological/blood
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Adrenergic beta-Antagonists); 9Y8NXQ24VQ (Propranolol); W980KJ009P (Corticosterone)
[Em] Entry month:1802
[Cu] Class update date: 180226
[Lr] Last revision date:180226
[Js] Journal subset:IM
[Da] Date of entry for processing:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191563

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[PMID]: 28453778
[Au] Autor:Caramaschi D; Sharp GC; Nohr EA; Berryman K; Lewis SJ; Davey Smith G; Relton CL
[Ad] Address:Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine.
[Ti] Title:Exploring a causal role of DNA methylation in the relationship between maternal vitamin B12 during pregnancy and child's IQ at age 8, cognitive performance and educational attainment: a two-step Mendelian randomization study.
[So] Source:Hum Mol Genet;26(15):3001-3013, 2017 08 01.
[Is] ISSN:1460-2083
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:An adequate intake of vitamin B12 during pregnancy plays an important role in offspring neurodevelopment, potentially via epigenetic processes. We used a two-step Mendelian randomization approach to assess whether DNA methylation plays a mediating and causal role in associations between maternal vitamin B12 status and offspring's cognition. Firstly, we estimated the causal effect of maternal vitamin B12 levels on cord blood DNA methylation using the maternal FUT2 genotypes rs492602:A > G and rs1047781:A > T as proxies for circulating vitamin B12 levels in the Avon Longitudinal Study of Parents and Children (ALSPAC) and we tested the observed associations in a replication cohort. Secondly, we estimated the causal effect of DNA methylation on IQ using the offspring genotype at sites close to the methylated CpG site as a proxy for DNA methylation in ALSPAC and in a replication sample. The first step Mendelian randomization estimated that maternal vitamin B12 had a small causal effect on DNA methylation in offspring at three CpG sites, which was replicated for one of the sites. The second step Mendelian randomization found weak evidence of a causal effect of DNA methylation at two of these sites on childhood performance IQ which was replicated for one of the sites. The findings support a causal effect of maternal vitamin B12 levels on cord blood DNA methylation, and a causal effect of vitamin B12-responsive DNA methylation changes on children's cognition. Some limitations were identified and future studies using a similar approach should aim to overcome such issues.
[Mh] MeSH terms primary: Intelligence/drug effects
Prenatal Exposure Delayed Effects/genetics
Vitamin B 12/metabolism
[Mh] MeSH terms secundary: Adult
Child
Cognition/drug effects
DNA Methylation/genetics
DNA Methylation/physiology
Epigenesis, Genetic/genetics
Family
Female
Fetal Blood/metabolism
Genotype
Humans
Intelligence Tests
Longitudinal Studies
Male
Mendelian Randomization Analysis
Pregnancy
Prenatal Exposure Delayed Effects/metabolism
Random Allocation
[Pt] Publication type:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:P6YC3EG204 (Vitamin B 12)
[Em] Entry month:1801
[Cu] Class update date: 180225
[Lr] Last revision date:180225
[Js] Journal subset:IM
[Da] Date of entry for processing:170429
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddx164

  9 / 25081 MEDLINE  
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[PMID]: 29315373
[Au] Autor:Wang Z; Shen M; Xue P; DiVall SA; Segars J; Wu S
[Ad] Address:Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
[Ti] Title:Female Offspring From Chronic Hyperandrogenemic Dams Exhibit Delayed Puberty and Impaired Ovarian Reserve.
[So] Source:Endocrinology;159(2):1242-1252, 2018 02 01.
[Is] ISSN:1945-7170
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Female offspring of many species exposed to high doses of androgens in utero experience endocrine dysfunction during adulthood. The phenotype of offspring from females with prepregnancy hyperandrogenemia and impaired ovulation, however, has not been examined. We developed a mouse model of hyperandrogenemia by implanting a low-dose dihydrotestosterone (DHT) pellet 15 days before conception. Female offspring born to dams with hyperandrogenemia (DHT daughters) had delayed puberty (P < 0.05) with first estrus on postnatal day (PND) 41 compared with daughters from dams with physiological levels of DHT (non-DHT daughters, PND37.5). Serum follicle-stimulating hormone (FSH) levels in the DHT daughters were fourfold higher (P < 0.05) on PND21, and anti-Müllerian hormone levels were higher (P < 0.05) on PND26 than in non-DHT daughters (controls). DHT daughters showed an extended time in metestrus/diestrus and a shorter time in the proestrus/estrus phase compared with non-DHT daughters (P < 0.05). To examine ovarian response to gonadotropins, superovulation was induced and in vitro fertilization (IVF) was performed. Fewer numbers of oocytes were retrieved from the DHT daughters compared with non-DHT daughters (P < 0.05). At IVF, there was no difference in rates of fertilization or cleavage of oocytes from either group. There were fewer (P < 0.01) primordial follicles (6.5 ± 0.8 vs 14.5 ± 2.1 per ovary) in the ovaries of DHT daughters compared with non-DHT daughters. Daughters from hyperandrogenemic females exhibited elevated prepubertal FSH levels, diminished ovarian response to superovulation, impaired estrous cyclicity, delayed onset of puberty, and reduced ovarian reserve, suggesting that fetal androgen exposure had lasting effects on female reproductive function.
[Mh] MeSH terms primary: Hyperandrogenism
Ovarian Reserve/physiology
Prenatal Exposure Delayed Effects
Primary Ovarian Insufficiency/etiology
Sexual Maturation
[Mh] MeSH terms secundary: Animals
Cells, Cultured
Chronic Disease
Female
Fertility
Hyperandrogenism/complications
Hyperandrogenism/physiopathology
Male
Mice
Mice, Inbred C57BL
Pregnancy
Prenatal Exposure Delayed Effects/physiopathology
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1802
[Cu] Class update date: 180223
[Lr] Last revision date:180223
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180110
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-03078

  10 / 25081 MEDLINE  
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[PMID]: 29309562
[Au] Autor:Rashid CS; Lien YC; Bansal A; Jaeckle-Santos LJ; Li C; Won KJ; Simmons RA
[Ad] Address:Center for Research on Reproduction and Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
[Ti] Title:Transcriptomic Analysis Reveals Novel Mechanisms Mediating Islet Dysfunction in the Intrauterine Growth-Restricted Rat.
[So] Source:Endocrinology;159(2):1035-1049, 2018 02 01.
[Is] ISSN:1945-7170
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Intrauterine growth restriction (IUGR) increases the risk of type 2 diabetes developing in adulthood. In previous studies that used bilateral uterine artery ligation in a rat model of IUGR, age-associated decline in glucose homeostasis and islet function was revealed. To elucidate mechanisms contributing to IUGR pathogenesis, the islet transcriptome was sequenced from 2-week-old rats, when in vivo glucose tolerance is mildly impaired, and at 10 weeks of age, when rats are hyperglycemic and have reduced ß-cell mass. RNA sequencing and functional annotation with Ingenuity Pathway Analysis revealed temporal changes in IUGR islets. For instance, gene expression involving amino acid metabolism was significantly reduced primarily at 2 weeks of age, but ion channel expression, specifically that involved in cell-volume regulation, was more disrupted in adult IUGR islets. Additionally, we observed alterations in the microenvironment of IUGR islets with extracellular matrix genes being significantly increased at 2 weeks of age and significantly decreased at 10 weeks. Specifically, hyaluronan synthase 2 expression and hyaluronan staining were increased in IUGR islets at 2 weeks of age (P < 0.05). Mesenchymal stromal cell-derived factors that have been shown to preserve islet allograft function, such as Anxa1, Cxcl12, and others, also were increased at 2 weeks and decreased in adult islets. Finally, comparisons of differentially expressed genes with those of type 2 diabetic human islets support a role for these pathways in human patients with diabetes. Together, these data point to new mechanisms in the pathogenesis of IUGR-mediated islet dysfunction in type 2 diabetes.
[Mh] MeSH terms primary: Diabetes Mellitus, Type 2/etiology
Fetal Growth Retardation/genetics
Fetal Growth Retardation/metabolism
Islets of Langerhans/physiopathology
Pancreatic Diseases/etiology
Transcriptome
[Mh] MeSH terms secundary: Animals
Cells, Cultured
Female
Fetal Growth Retardation/physiopathology
Gene Expression Profiling
Humans
Pancreatic Diseases/genetics
Pancreatic Diseases/physiopathology
Pregnancy
Prenatal Exposure Delayed Effects/genetics
Prenatal Exposure Delayed Effects/metabolism
Prenatal Exposure Delayed Effects/physiopathology
Rats
Rats, Sprague-Dawley
Risk Factors
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Entry month:1802
[Cu] Class update date: 180223
[Lr] Last revision date:180223
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180109
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00888


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