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1.
Orv Hetil ; 161(2): 43-49, 2020 Jan.
Artigo em Húngaro | MEDLINE | ID: mdl-31902235

RESUMO

Hormonal imprinting is a physiological process, which is a part of the receptor-hormone complex development. It determines the binding capacity of the receptors across the lifespan. It takes place perinatally in the critical period of hormone receptor development, when the developmental window for imprinting is open and permits the binding of hormone-like molecules (related or synthetic hormones, endocrine disruptors etc.) causing disturbances of the endocrine system, and the systems- influenced organs by it, for life. This is the faulty hormonal imprinting. However, studying the medical database, PubMed, a lot of data can be found on the harmful late (adult age) effects of medication in the critical period of development with non-hormonal molecules, which are manifested later in functional alterations or diseases. This could mean that in the process of faulty imprinting, the openness of the developmental window could be more important than the structural similarity of a molecule to hormones. As developmentally critical period for faulty imprinting by hormone-like molecules is not exclusively the perinatal one (this is justified in the case of faulty hormonal imprinting), the pubertal period was also studied from this aspect and similarities to the impact of perinatal use have been found (this could be called "Pubertal Origin of Health and Disease = POHaD). While in the case of hormonal faulty imprinting, the mechanism seems to be clear (considering the role of receptors), the mechanism of drug-provoked imprinting is presently uncleared (considering the variety of medications which cause late-manifested alterations). The medicaments-caused faulty imprinting conception calls attention to the dangers of medication in the perinatal as well as the pubertal periods. Orv Hetil. 2020; 161(2): 43-49.


Assuntos
Disruptores Endócrinos/efeitos adversos , Impressão Genômica/efeitos dos fármacos , Hormônios/metabolismo , Sistema Endócrino , Feminino , Fertilização , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia
2.
Gut ; 69(1): 42-51, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036757

RESUMO

BACKGROUND AND AIMS: Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome. METHODS: We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines. RESULTS: Pregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in Gammaproteobacteria and depletion in Bifidobacteria. Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon. CONCLUSION: Aberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.


Assuntos
Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Complicações na Gravidez/microbiologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Imunidade Adaptativa , Adulto , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Disbiose/imunologia , Disbiose/microbiologia , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Feminino , Seguimentos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Vida Livre de Germes , Humanos , Recém-Nascido , Doenças Inflamatórias Intestinais/imunologia , Masculino , Troca Materno-Fetal , Gravidez , Complicações na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Estudos Prospectivos
3.
Equine Vet J ; 52(1): 136-143, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31009093

RESUMO

BACKGROUND: A recent study demonstrated that enrofloxacin and ciprofloxacin cross the equine placenta without causing gross cartilage or tendon lesions in the 9-month fetus; however, long-term effects of in utero fluoroquinolone exposure remain unknown. OBJECTIVES: To assess effects of fetal exposure to enrofloxacin on the resulting foal's cartilage and tendon strength. STUDY DESIGN AND METHODS: Healthy mares at 280 days' gestation were allocated into four groups: untreated (n = 5), therapeutic treatment (7.5 mg/kg enrofloxacin, PO × 14 days, n = 6), supratherapeutic treatment (15 mg/kg, PO × 14 days, n = 6) and no mare treatment with treatment of the foals post-partum (n = 2). Mares were allowed to carry pregnancy to term, and foals were maintained on pasture for 5 weeks. After that foals were euthanized, and their articular cartilage and extensor and flexor tendons were examined macroscopically and histologically for lesions. Tendon strength was tested by loading until failure. RESULTS: Administration of enrofloxacin at recommended doses in late gestation did not result in cartilaginous lesions or clinical lameness in any foal by 5 weeks old. Tensile strength was greater in hind tendons than front tendons, but no difference was found between foals born from treated and control mares. Expectedly, osteochondral changes were present both in foals born from enrofloxacin-treated mares and in negative control foals with no apparent association with fluoroquinolone treatment during pregnancy. MAIN LIMITATIONS: Only one time point in gestation was evaluated, and mares treated in the study were healthy at time of treatment. Additionally, it is possible that the assessments performed herein were not sensitive enough to detect subtle or functional changes in the articular cartilage. Further studies are needed to determine if enrofloxacin administration during late pregnancy potentiates osteochondral alterations in the first year of life. CONCLUSIONS: While this study did not assess other stages of gestation or long-term foal outcomes, short-term administration of enrofloxacin to late gestation mares did not result in macroscopic or microscopic lesions in the resulting foals by 5 weeks of age.


Assuntos
Enrofloxacina/efeitos adversos , Doenças dos Cavalos/etiologia , Complicações na Gravidez/veterinária , Prenhez , Animais , Animais Recém-Nascidos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Fenômenos Biomecânicos , Ciprofloxacino/efeitos adversos , Ciprofloxacino/metabolismo , Relação Dose-Resposta a Droga , Enrofloxacina/administração & dosagem , Feminino , Cavalos , Gravidez , Complicações na Gravidez/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Tendões/efeitos dos fármacos , Tendões/patologia
4.
BJOG ; 127(1): 39-45, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31444892

RESUMO

OBJECTIVE: To explore the relation between famine exposure in early life and subsequent pregnancy loss, including stillbirth, and spontaneous abortion in adulthood. DESIGN: A population-based, partly ecological study. SETTING AND POPULATION: Individual data of 58 601 females born around the time of the Great Chinese Famine in 1959-1961. METHODS: Associations between the famine exposure in early life and pregnancy loss (stillbirth and spontaneous abortion) in adulthood were analysed using negative binomial regression, with the non-exposure group as reference, adjusting for region, highest education, monthly income, alcohol consumption, tobacco use, body mass index in 25-year-olds and metabolic equivalent. Further analyses were stratified by rural versus urban region. MAIN OUTCOME MEASURES: Continuous variables of times of stillbirths and spontaneous abortions were used according to the individual self-reported reproductive history. RESULTS: No association was found between famine exposure and spontaneous abortion. In contrast, females experiencing the famine during their prenatal period (incidence rate ratio = 1.15, 95% CI 1.00-1.33) or infant period (incidence rate ratio = 1.27, 95% CI 1.12-1.44) were more likely to report stillbirth in later adult life. Such an association appeared stronger in women living in rural regions. CONCLUSIONS: Early life exposure of famine was associated with an increased risk of stillbirth but not spontaneous abortion in adulthood. The strength of such an association appeared stronger in rural areas. Given the high potential for unmeasured confounding, these associations must be interpreted with caution. Regarding the potential implication that undernutrition in the fetal period is related to reproductive outcome in adulthood, fetal nutritional supply may play an important role in human reproduction. TWEETABLE ABSTRACT: Exposure to famine in early life was associated with increased pregnancy loss in adulthood.


Assuntos
Aborto Espontâneo/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Natimorto/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Gravidez , Saúde da População Rural
5.
BJOG ; 127(1): 8-16, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31529594

RESUMO

BACKGROUND: With expanding recreational cannabis legalisation, pregnant women and their offspring are at risk of potentially harmful consequences. OBJECTIVES: To assess the prevalence of recreational cannabis use among pregnant women, health outcomes associated with prenatal recreational cannabis use, and the potential impact of recreational cannabis legalisation on this population. SEARCH STRATEGY: Five databases and the grey literature were systematically searched (2000-2019). SELECTION CRITERIA: Human studies published in English or French reporting on the prevalence of prenatal recreational cannabis use in high-income countries. DATA COLLECTION AND ANALYSIS: Data on study characteristics, prenatal substance use, and health outcomes were extracted and qualitatively synthesised. MAIN RESULTS: Forty-one publications met our inclusion criteria. The overall prevalence of prenatal cannabis use varied substantially (min-max: 0.24-22.6%), with the greatest use in the first trimester. In the three studies with temporal data available, rates of prenatal cannabis use increased across years. Only 7/41 and 5/41 studies provided information on gestational age of exposure and frequency of use, respectively. The concomitant use of alcohol, illicit drugs, and tobacco was higher among cannabis users than nonusers. Prenatal cannabis use was associated with select neonatal, but not maternal, health outcomes. There were insufficient data to compare prenatal cannabis use between the pre- and post-legalisation periods. CONCLUSION: Cannabis use among pregnant women is prevalent and may be associated with adverse neonatal outcomes. Future studies should assess the gestational age and frequency of cannabis exposure, and usage patterns prior to and following legalisation. TWEETABLE ABSTRACT: Women who consume cannabis during pregnancy could risk predisposing their newborns to poor birth outcomes.


Assuntos
Uso da Maconha/efeitos adversos , Complicações na Gravidez/etiologia , Países Desenvolvidos , Métodos Epidemiológicos , Feminino , Idade Gestacional , Humanos , Renda , Recém-Nascido de Baixo Peso , Terapia Intensiva Neonatal/estatística & dados numéricos , Uso da Maconha/epidemiologia , Uso da Maconha/legislação & jurisprudência , Saúde Materna , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia
6.
Ideggyogy Sz ; 72(9-10): 325-336, 2019 Sep 30.
Artigo em Húngaro | MEDLINE | ID: mdl-31625699

RESUMO

With the acceptance of "The developmental origins of health and disease" concept in the 1990s, it became clear that epigenetic inheritance, which do not involve changes in the DNA sequence has important role in the pathogenesis of diseases. Epigenetic regulation serves the adaptation to the changing environment and maintains the reproductive fitness even on the drawback of increased risk of diseases in later life. The role of epigenetic mechanisms in chronic non-communicable diseases has been well established. Recent studies have revealed that epigenetic changes have also causal role in certain pediatric diseases. The review evaluates the recent epigenetic findings in the pathomechanism of common pediatric diseases. The wide range and long-lasting duration of epigenetic regulations give importance to the subject. Methods are already available to evaluate a part of the epigenetic changes in the clinical practice, presently aiming primarily the estimation of the disease risk or definition of diagnosis. Furthermore, there are already available limited means to influence the epigenetic regulation.


Assuntos
Metilação de DNA/fisiologia , Epigênese Genética , Cardiopatias , Transtornos Mentais , Doenças Metabólicas , Efeitos Tardios da Exposição Pré-Natal , Criança , Pré-Escolar , Metilação de DNA/genética , Feminino , Cardiopatias/genética , Humanos , Transtornos Mentais/genética , Doenças Metabólicas/genética , Pediatria , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética
7.
Sheng Li Xue Bao ; 71(5): 749-759, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646329

RESUMO

With the evolution of medical techniques and technology, an increasing number of infants, neonates, and fetuses are exposed to general anesthesia for clinical diagnostic and therapeutic process. The neurotoxic effects of general anesthetics on developing brain have been a subject of concern and considerable research interest. Population-based study confirmed that single short-term general anesthetic exposure does not affect nervous system function, but multiple exposures to general anesthesia could damage cognitive function. Animal studies further discovered the underlying mechanisms. Nervous system is most susceptible to general anesthetics during the brain growth spurt. The time-point is more critical than the duration of exposure to general anesthetics. General anesthetics can induce intracellular calcium overload, disturb energy metabolism, promote cell apoptosis and lead to cell loss. General anesthetics can damage synaptic structure, transmission and plasticity, and impair brain function. High throughput omics technologies have been used to screen the differentially expressed genes induced by general anesthetics, which provide further understanding of the mechanism of general anesthetics affecting cognitive function. This review provides an update on the pathophysiologic mechanisms underlying the anesthesia-neurotoxicity, which will be helpful to provide instructions for the clinical use of general anesthesia in children.


Assuntos
Anestésicos Gerais/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Cognição , Anestesia Geral/efeitos adversos , Animais , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia
9.
Chem Biol Interact ; 312: 108792, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31491373

RESUMO

Cadmium (Cd) is an important toxic chemical due to its increasing levels in the environment and bioaccumulation in humans and animals. The present study was performed to evaluate the effects of long-term exposure to 1, 10, or 100 µg/L Cd in drinking water on the development, reproduction and neurotoxicity of offspring when administered to mice from parental puberty to postnatal 10 weeks in offspring. The development parameters measured in offspring included physical development, reflex ontogeny, body weight and body size. The reproductive indices measured consisted of anogenital distances (AGDs), estrous cycle, sperm quality, specific gene expression in Leydig or Sertoli cells, seminiferous epithelium cycle, sex hormone levels, histological morphology and apoptosis in testis or ovary, and the levels of oxidative stress. The determination of neurotoxicity included learning and memory ability, anxiety, and related serum indicators. In addition, blood lipid level, liver and kidney function were also determined by serum biochemical assays. The results showed that exposure to Cd in the present model had no adverse effects on development, but had some reproductive toxicity and neurotoxicity, including alteration of spermatogenic epithelial staging in testis and inducing anxiety in offspring. Furthermore, the levels of total protein, globulins, total bile acid and direct bilirubin were also significantly altered, especially in female offspring. The present study suggested that long-term exposure to low doses of Cd had adverse effects on the health of the next generation, and some harmful effects showed gender differences in offspring. The present study demonstrated that attention should be paid to Cd pollution in the environment, especially before pregnancy.


Assuntos
Cádmio/toxicidade , Reprodução/efeitos dos fármacos , Animais , Análise Química do Sangue , Feminino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia
11.
Klin Padiatr ; 231(5): 262-268, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31505693

RESUMO

OBJECTIVE: The consumption of illegal substances during pregnancy is an increasing social and medical issue. Main substances of prenatal drug exposure are beside tehtrahydrocannabinol (THC), opioids and methamphetamine. The effect of these substances on the long-term development of children remains uncertain. METHODS: Since 2012 newborn infants born at the university hospital of children at Leipzig which were prenatal exposed to drugs were followed long-term at the out-patient clinic for child protection. For 42 children with prenatal opioid or methamphetamine exposure the developmentent was analysed using the Bayley Scales (BSID III) at the age of 2-3 years. The children were compared with 84 unexposed control children. One case matched to 2 controls, adapted by age, gender, gestational age and birth weight. RESULTS: Motoric development between prenatal methylamphetamine, opioid exposed children and the control group showed no significant difference. Methylamphetamine exposed children (n=23) At 2 exposure show significantly lower scores in cognition and language (79,1 compared 95,9 of the control group), opioid exposed children have a slight cognitive deficits with a medium score of 91,7 (n=19). 56% of the methamphetamine group were developmentally retarded at the measurement date. Additionally, children had significant lower Bayley Scores which had single parent and/ or low educational and professional qualifications of their caregiver. Both substances increased the risk of postnatal complications to 46-53% despite of similar gestational ages in all groups. CONCLUSION: Children with prenatal methamphetamine or opioid exposure seem to have cognition and language deficits at 2 and 3 years of age. Methamphetamine might have a higher negative effect than opioids. The psychosocial risk factors associated with parental drug abuse are important for achieving age-appropriate development.


Assuntos
Analgésicos Opioides/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Metanfetamina/toxicidade , Atividade Motora/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Comportamento do Lactente/efeitos dos fármacos , Comportamento do Lactente/psicologia , Recém-Nascido , Linguagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia
12.
Environ Sci Technol ; 53(20): 12026-12034, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525872

RESUMO

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.


Assuntos
Citocromo P-450 CYP2E1 , Efeitos Tardios da Exposição Pré-Natal , Biomarcadores , Peso ao Nascer , Desinfecção , Feminino , Glutationa Transferase , Humanos , Exposição Materna , Polimorfismo Genético , Gravidez , Trialometanos
13.
BJOG ; 126(13): 1588-1597, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31529591

RESUMO

OBJECTIVE: To examine the association of prenatal alcohol exposure (PAE) on cognitive abilities and behaviour profiles of 4-year-old children. DESIGN: Prospective cohort study. SETTING: Cape Town, South Africa. POPULATION: A cohort of 500 children. METHODS: Children from the Safe Passage Study, which prospectively collected PAE, were included. Cognition and behavioural profiles were assessed. Children with and without PAE were compared. Mean scores were compared, with P ≤ 0.05 considered significant. Results were adjusted for confounding factors. MAIN OUTCOME MEASURES: The Kaufman Assessment Battery for children measured intellectual and mental ability; the NEPSY-II instrument assessed neurocognitive performance. The caregiver completed the Preschool Child Behaviour checklist to rate the child's problem behaviours and competencies. RESULTS: Two hundred children had no PAE, 117 children had mild to moderate PAE (with no binge episodes), 113 children had heavy PAE (with one or two binge episodes), and 70 children had very heavy PAE (with three or more binge episodes). Women who binge drank had significantly higher rates of smoking, marijuana use, and methamphetamine use. Low to moderate PAE had no effect on cognitive ability and behaviour. Very heavy PAE was associated with problems performing simultaneous as well as sequential functions, lower scores in the language and sensorimotor domain, and more attention and pervasive developmental problems. CONCLUSIONS: Low to moderate PAE was not associated with cognitive processing or developmental problems. Women who had many binge drinking episodes during pregnancy were the most at risk for cognitive processing, neurocognitive, and behaviour problems in their children at 4 years of age. TWEETABLE ABSTRACT: Low to moderate prenatal alcohol use was not associated with cognitive or behavioural problems in 4-year-olds.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Desenvolvimento Infantil/fisiologia , Transtornos do Neurodesenvolvimento/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Pré-Escolar , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Testes Neuropsicológicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , África do Sul/epidemiologia
14.
Toxicol Lett ; 316: 136-146, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520701

RESUMO

Prenatal dexamethasone exposure (PDE) induces developmental toxicities of multiple organs in offspring, but its serum metabolic profile changes before and after birth are unclear. Here, we employed a LC-MS-based metabolomic approach to detect serum metabolites of PDE offspring rats in utero and adulthood, and explore its change characteristics and toxicological significances. Meanwhile, the bodyweight, serum index related to hepatic and renal function were detected. As compared to healthy control rats, PDE reduced offspring birthweight but caused postnatal catch-up growth accompanied by adult liver and kidney function injury. In utero, the differential metabolites in response to PDE were mainly manifested as enhanced glycolysis, increased protein breakdown and disordered lipid metabolism, and multiple metabolic pathways were changed, which displayed gender differences. In adulthood, PDE offspring showed fewer and inconsistent types of differential metabolites compared to those in utero, which exhibited significant gender differences. The main differential metabolites induced by PDE included lactic acid, carnitine, cortexolone, bile acid, phosphatidylcholine, uric acid and platelet activating factor, which may participate in dexamethasone multi-organ toxicities and multi-disease susceptibility. In conclusion, PDE could induce a gender-difference and sustainable multi-organ damage in the offspring rats via serum metabolic profile analysis, which will enhance offspring susceptibility to multiple adult diseases.


Assuntos
Dexametasona/toxicidade , Metabolismo Energético/efeitos dos fármacos , Glucocorticoides/toxicidade , Metabolômica/métodos , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Animais , Animais Recém-Nascidos , Biomarcadores/sangue , Peso ao Nascer/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Dexametasona/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Gravidez , Ratos Wistar , Medição de Risco , Fatores Sexuais , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Fatores de Tempo
15.
Bioelectromagnetics ; 40(7): 498-511, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522469

RESUMO

Despite much research, gaps remain in knowledge about the potential health effects of exposure to radiofrequency (RF) fields. This study investigated the effects of early-life exposure to pulsed long term evolution (LTE) 1,846 MHz downlink signals on innate mouse behavior. Animals were exposed for 30 min/day, 5 days/week at a whole-body average specific energy absorption rate (SAR) of 0.5 or 1 W/kg from late pregnancy (gestation day 13.5) to weaning (postnatal day 21). A behavioral tracking system measured locomotor, drinking, and feeding behavior in the home cage from 12 to 28 weeks of age. The exposure caused significant effects on both appetitive behaviors and activity of offspring that depended on the SAR. Compared with sham-exposed controls, exposure at 0.5 W/kg significantly decreased drinking frequency (P ≤ 0.000) and significantly decreased distance moved (P ≤ 0.001). In contrast, exposure at 1 W/kg significantly increased drinking frequency (P ≤ 0.001) and significantly increased moving duration (P ≤ 0.005). In the absence of other plausible explanations, it is concluded that repeated exposure to low-level RF fields in early life may have a persistent and long-term effect on adult behavior. Bioelectromagnetics. 2019;40:498-511. © 2019 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Ondas de Rádio/efeitos adversos , Animais , Comportamento Animal/efeitos da radiação , Peso Corporal/efeitos da radiação , Simulação por Computador , Feminino , Aprendizagem/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Fatores de Tempo , Irradiação Corporal Total
16.
MMWR Morb Mortal Wkly Rep ; 68(36): 777-783, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31513558

RESUMO

Since 1999, the rate of opioid use disorder (OUD) has more than quadrupled, from 1.5 per 1,000 delivery hospitalizations to 6.5 (1), with similar increases in incidence of neonatal abstinence syndrome (NAS) observed for infants (from 2.8 per 1,000 live births to 14.4) among Medicaid-insured deliveries (2). CDC's response to the opioid crisis involves strategies to prevent opioid overdoses and related harms by building state capacity and supporting providers, health systems, and payers.* Recognizing systems gaps in provision of perinatal care and services, CDC partnered with the Association of State and Territorial Health Officials (ASTHO) to launch the Opioid Use Disorder, Maternal Outcomes, and Neonatal Abstinence Syndrome Initiative Learning Community (OMNI LC). OMNI LC supports systems change and capacity building in 12 states.† Qualitative data from participating states were analyzed to identify strategies, barriers, and facilitators for capacity building in state-defined focus areas. Most states focused on strategies to expand access to and coordination of quality services (10 of 12) or increase provider awareness and training (nine of 12). Fewer states focused on data, monitoring, and evaluation (four of 12); financing and coverage (three of 12); or ethical, legal, and social considerations (two of 12). By building capacity to strengthen health systems, state-identified strategies across all focus areas might improve the health trajectory of mothers, infants, and families affected by the U.S. opioid crisis.


Assuntos
Síndrome de Abstinência Neonatal/terapia , Transtornos Relacionados ao Uso de Opioides/terapia , Complicações na Gravidez/terapia , Efeitos Tardios da Exposição Pré-Natal/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Síndrome de Abstinência Neonatal/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Período Pós-Parto , Gravidez , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estados Unidos/epidemiologia
17.
Endocrinology ; 160(10): 2471-2484, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398247

RESUMO

Prenatal testosterone (T)-treated sheep, similar to women with polycystic ovary syndrome (PCOS), manifest oligo-/anovulation, hyperandrogenism, and polyfollicular ovary. The polyfollicular ovarian morphology, a result of persistence of antral follicles, arises, in part, by transcriptional changes in key mediators of follicular development that, in turn, are driven by epigenetic mechanisms. We hypothesized that prenatal T excess induces, in a cell-specific manner, transcriptional changes in key mediators of follicular development associated with relevant changes in epigenetic machinery. Expression levels of key mediators of follicular development, DNA methyltransferases (DNMTs), and histone de-/methylases and de-/acetylases were determined in laser-capture microdissection-isolated antral follicular granulosa and theca and ovarian stromal cells from 21 months of age control and prenatal T-treated sheep (100 mg IM twice weekly from gestational day 30 to 90; term: 147 days). Changes in histone methylation were determined by immunofluorescence. Prenatal T treatment induced the following: (i) cell-specific changes in gene expression of key mediators of follicular development and steroidogenesis; (ii) granulosa, theca, and stromal cell-specific changes in DNMTs and histone de-/methylases and deacetylases, and (iii) increases in histone 3 trimethylation at lysine 9 in granulosa and histone 3 dimethylation at lysine 4 in theca cells. The pattern of histone methylation was consistent with the expression profile of histone de-/methylases in the respective cells. These findings suggest that changes in expression of key genes involved in the development of the polyfollicular phenotype in prenatal T-treated sheep are mediated, at least in part, by cell-specific changes in epigenetic-modifying enzymes.


Assuntos
Epigênese Genética/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Síndrome do Ovário Policístico/veterinária , Doenças dos Ovinos/induzido quimicamente , Propionato de Testosterona/toxicidade , Animais , Feminino , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ovinos , Doenças dos Ovinos/metabolismo
18.
Life Sci ; 233: 116741, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31398419

RESUMO

AIMS: Carbon black nanoparticles (CBNPs) are widely used in industrial field. Sensitive stages such as pregnancy are assumed to be more susceptible to stimulus, however whether pregnancy exposure to CBNPs (PrE-to-CBNPs) would cause long-term toxic effects in dams and the underlying mechanisms remain poorly addressed. The present study is aimed to determine the long-term toxic effects of PrE-to-CBNPs in dams. MATERIALS AND METHODS: The pregnant mice were randomly divided into control group, low (21 µg/animal), medium (103 µg/animal) and high (515 µg/animal) CBNPs-treated groups. From gestational day (GD) 9 to GD18, the pregnant mice were intranasal exposed. At 49 days after parturition, lung tissues and bronchoalveolar lavage fluid (BALF) were obtained. Weight change, lung histopathology, lung ultrastructural pathology, cell count in BALF, oxidative stress/inflammatory maker and autophagy/lysosome-related protein expression were determined. KEY FINDINGS: PrE-to-CBNPs caused a dose-dependent persistent lung injury in mice even 49 days after parturition, including the deteriorative lung histopathological changes, elevation of oxidative stress marker Nrf-2, HO-1 and CHOP, infiltration of macrophage and increased mRNA expression of inflammatory cytokines in the lung tissues and elevation of cells in BALF. However, PrE-to-CBNPs did not induce significant neutrophil infiltration and fibrosis. Moreover, we found that CBNPs could deposit in the lysosomes and decrease cathepsin D (an important hydrolase in lysosome), which might be associated with the dysfunction of lysosome and autophagy. SIGNIFICANCE: Our study demonstrated that PrE-to-CBNPs could result in long-term lung injury in dams, and lysosomal dysfunction was probably linked to this process.


Assuntos
Inflamação/complicações , Lesão Pulmonar/etiologia , Lisossomos/patologia , Nanopartículas/efeitos adversos , Estresse Oxidativo , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fuligem/efeitos adversos , Animais , Autofagia , Citocinas/metabolismo , Feminino , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia
19.
Ecotoxicol Environ Saf ; 183: 109544, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31400720

RESUMO

Cigarette smoke can affect female reproductive health by causing follicle destruction and oocyte dysfunction. Third-hand smoke has received increasing attention as a public health issue. However, the effects of third-hand smoke on the female reproductive system, particularly the ovaries, remain unclear. 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA) can be used as a biomarker of third-hand smoke. We studied the in vivo toxic effects of NNA on mice ovaries and offspring development. Three-week-old premature female mice were exposed to NNA at two different concentrations (0.075 µg/kg and 0.15 µg/kg body weight) and tap water (blank control) and diluted dimethylsulfoxide (solvent control) for 30 days. We found that oral administration of NNA (0.075 µg/kg and 0.15 µg/kg) significantly reduced ovary weight (the 0.15 µg/kg group was reduced to 18.69% ±â€¯0.89%) and ovarian follicle number (reduced by about 30%) (p < 0.05). Consumption of 0.15 µg/kg NNA reduced the survival rate of superovulated oocytes from 91.36% to 60.55% (p < 0.05). In addition, treated female mice in each group were mated with normal male mice to observe the effects of NNA on the F1 offspring, and during mating and lactation, all groups were given tap water. Two different concentrations of NNA exposure also significantly reduced body weight and impaired ear opening, tooth eruption and eye opening in F1 offspring, especially those exposed to 0.15 µg/kg NNA (p < 0.05). Our study suggested that NNA exposure had toxic effects on the reproductive health of female mice and their offspring. The results obtained may help evaluate the risks of third-hand smoke to women's reproductive health and to the health of their offspring.


Assuntos
Aldeídos/toxicidade , Ovário/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Piridinas/toxicidade , Reprodução/efeitos dos fármacos , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Lactação , Masculino , Camundongos , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Tabaco/química
20.
Toxicol Lett ; 315: 87-95, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31425726

RESUMO

Prenatal alcohol exposure (PAE) is often associated with congenital heart defects, most commonly septal, valvular, and great vessel defects. However, there have been no known studies on whether PAE affects the resulting fibroblast population after development, and whether this has any consequences in the postnatal period. Our previous study focused on the effects of PAE on the postnatal fibroblast population, which translated into changes in cardiac extracellular matrix (ECM) composition and cardiac function in the neonatal heart. Moreover, our lab has previously demonstrated that alcohol-induced fibrosis is mediated by oxidative stress mechanisms in adult rat hearts following chronic alcohol exposure. Thus, we hypothesize that PAE alters cardiac ECM composition that persists into the postnatal period, leading to cardiac dysfunction, and these effects are prevented by antioxidant treatment. To investigate these effects, pregnant mice were intraperitoneally injected with 2.9 g EtOH/kg body weight on gestation days 6.75 and 7.25. Controls were injected with vehicle saline. Randomly selected dams in both groups were then treated with 100 mg/kg body weight of the antioxidant N-acetylcysteine (NAC) immediately after EtOH or vehicle administration. Left ventricular (LV) chamber dimension and function were assessed in sedated animals on neonatal day 5 using echocardiography. Ejection fraction decreased in the PAE group. NAC treatment prevented this depression of systolic function in PAE neonates. Hearts were analyzed for expression of fibroblast activation markers. Alpha smooth muscle actin (α-SMA) increased in PAE neonatal hearts, and this increase was prevented by NAC treatment. In PAE pups, collagen I decreased, but collagen III expression increased compared to saline animals; the overall collagen I/III ratio significantly decreased. When PAE mice were treated with NAC, collagen I/III ratio did not change. Overall, our data demonstrate that prenatal alcohol exposure produces changes in collagen subtype in neonatal cardiac ECM and a decline in systolic function, and these adverse effects were prevented by NAC treatment.


Assuntos
Acetilcisteína/farmacologia , Alcoolismo/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Vasos Coronários/química , Etanol/toxicidade , Fibroblastos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Camundongos , Gravidez
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