Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.301
Filtrar
1.
Chem Biol Interact ; 323: 109076, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32240654

RESUMO

A growing body of evidence indicates that exposure to nonylphenol (NP), a typical persistent organic pollutant (POP), in early life results in the impairment of the central nervous system (CNS), but the underlying mechanism still remains to be elucidated. High levels of pro-inflammatory cytokines in the brain have been implicated in the CNS damages. The animal model of exposure to NP in early life was established by maternal gavage during the pregnancy and lactation in the present study. We found that exposure to NP in early life increased the levels of pro-inflammatory cytokines in the rat prefrontal cortex. Interestingly, the levels of pro-inflammatory cytokines in the intestine as well as in the serum were also increased by NP exposure. Furthermore, the increased permeability of intestinal barrier and blood-brain barrier (BBB), two critical barriers in the gut to brain communication, was observed in the rats exposed to NP in early lives. The decreased expression of zonula occludens-1 (ZO-1) and claudin-1 (CLDN-1), tight junction proteins (TJs) that responsible for maintaining the permeability of intestinal barrier and BBB, was found, which may underlie these increases in permeability. Taken together, these results suggested that the disturbed gut-brain communication may contribute to the increased levels of pro-inflammatory cytokines in the prefrontal cortex caused by NP exposure in early life.


Assuntos
Citocinas/metabolismo , Trato Gastrointestinal/patologia , Mediadores da Inflamação/metabolismo , Fenóis/toxicidade , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Animais Recém-Nascidos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Líquido Cefalorraquidiano/metabolismo , Claudina-1/metabolismo , Citocinas/sangue , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Mediadores da Inflamação/sangue , Intestinos/efeitos dos fármacos , Intestinos/patologia , Exposição Materna , Permeabilidade , Córtex Pré-Frontal/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Ratos Sprague-Dawley , Proteína da Zônula de Oclusão-1/metabolismo
2.
PLoS One ; 15(2): e0229434, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32109947

RESUMO

The main goal of this manuscript was to investigate the neurodevelopment of children exposed by Zika virus in the intrauterine period who are asymptomatic at birth. Newborns with documented Zika virus exposure during the intrauterine period who were asymptomatic at birth were followed in the first two years of life for neurodevelopment using Bayley III test. Children were classified as having normal or delayed neurodevelopment for age based on most recent Bayley III evaluation results. Eighty-four infants were included in the study. The first Bayley III evaluation was performed at a mean chronological age of 9.7±3.1 month; 13 children (15%) had a delay in one of the three domains, distributed as follow: 10 (12%) in the language domain and 3 (3.5%) in the motor domain. The most recent Bayley III evaluation was performed at a mean age 15.3±3.1 months; 42 children (50%) had a delay in one of the three domains: 4 (5%) in cognition, 31 (37%) in language, and 20 (24%) in motor performance. There were no statistical differences in Gender, Gestational Age, Birth Weight and Head Circurference at birth between children with normal and delayed neurodevelopment for age. A very high proportion of children exposed ZIKV during pregnancy who were asymptomatic at birth demonstrated a delay in neurodevelopment, mainly in the language domain, the first two years of life.


Assuntos
Transtornos do Neurodesenvolvimento/etiologia , Complicações Infecciosas na Gravidez/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Útero/virologia , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Adolescente , Adulto , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Transtornos do Neurodesenvolvimento/patologia , Parto , Gravidez , Complicações Infecciosas na Gravidez/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Adulto Jovem , Infecção por Zika virus/virologia
3.
PLoS One ; 15(1): e0226605, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995614

RESUMO

The placenta plays a central role in the epigenetic programming of neurodevelopment by prenatal stress (PS), but this pathway is not fully understood. It difficult to study in humans because the conditions for intense, traumatic PS are almost impossible to create ethically. This study was able to capitalize on a 2012 disaster that hit New York, Superstorm Sandy, to examine the impact of traumatic stress on placental gene expression while also examining normative PS, and compare the two. Of the 303 expectant mothers participating in the Stress in Pregnancy Study, 95 women were pregnant when Superstorm Sandy struck. During their pregnancy, participants completed self-report measures of PS and distress that were combined, using latent profile analysis, into one global indicator of normative PS. Placental tissue was collected at delivery and frozen for storage. RNA expression was assessed for 40 placental genes known to associate with the stress response system and neurodevelopment in offspring. Results showed that normative PS increased expression of just MECP2, HSD11B2, and ZNF507, whereas Superstorm Sandy PS decreased expression of CDKL5, CFL1, DYRK1A, HSD11B2, MAOA, MAOB, NCOR1, and ZNF507. Interaction analyses indicated that Superstorm Sandy PS was associated with decreased gene expression for the low and high PS group for CFL1, DYRK1A, HSD11B2, MAOA, and NCOR1 and increased expression for the moderate PS group for FOXP1, NR3C1, and NR3C2. This study supports the idea that a moderate amount of normative PS may buffer the impact of traumatic PS, in this case caused by Superstorm Sandy, on placental gene expression, which suggests that the placenta itself mirrors the organism's ability to develop an epigenetic resilience to, and inoculation from, stress.


Assuntos
Tempestades Ciclônicas , Regulação da Expressão Gênica no Desenvolvimento , Exposição Materna/efeitos adversos , Placenta/metabolismo , Proteínas da Gravidez/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Estresse Psicológico , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Proteínas da Gravidez/metabolismo , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/patologia
4.
Am J Pathol ; 190(2): 295-305, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31837289

RESUMO

Preterm birth (PTB) affects nearly 15 million infants each year. Of these PTBs, >25% are a result of inflammation or infection. Animal models have improved our understanding of the mechanisms leading to PTB. Prior work has described induction of intrauterine inflammation in mice with a single injection of lipopolysaccharide (LPS). Herein, we have improved the reproducibility and potency of LPS in the model using two injections distal to the cervix. An in vivo imaging system revealed more uniform distribution of Evans Blue Dye using a double distal injection (DDI) approach compared with a single proximal injection (SPI). Endotoxin concentrations in vaginal lavage fluid from SPI dams were significantly higher than from DDI dams. At equivalent LPS doses, DDI consistently induced more PTB than SPI, and DDI showed a linear dose-response, whereas SPI did not. Gene expression in myometrial tissue revealed increased levels of inflammatory markers in dams that received LPS DDI compared with LPS SPI. The SPI group showed more significant overexpression in cervical remodeling genes, likely due to the leakage of LPS from the uterine horns through the cervix. The more reliable PTB induction and uniform uterine exposure provided by this new model will be useful for further studying fetal outcomes and potential therapeutics for the prevention of inflammation-induced PTB.


Assuntos
Modelos Animais de Doenças , Inflamação/complicações , Lipopolissacarídeos/toxicidade , Miométrio/patologia , Nascimento Prematuro/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Animais , Feminino , Inflamação/induzido quimicamente , Inflamação/patologia , Camundongos , Miométrio/efeitos dos fármacos , Miométrio/imunologia , Gravidez , Nascimento Prematuro/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Útero/efeitos dos fármacos
5.
Am J Physiol Lung Cell Mol Physiol ; 318(2): L407-L418, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31644311

RESUMO

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.


Assuntos
Antibacterianos/efeitos adversos , Displasia Broncopulmonar/complicações , Lesão Pulmonar/induzido quimicamente , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/patologia , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Líquido da Lavagem Broncoalveolar , Displasia Broncopulmonar/fisiopatologia , Citocinas/metabolismo , Feminino , Granulócitos/metabolismo , Hiperóxia/complicações , Hiperóxia/fisiopatologia , Inflamassomos/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Pulmão/patologia , Lesão Pulmonar/microbiologia , Lesão Pulmonar/fisiopatologia , Camundongos Endogâmicos C57BL , Oxigênio/metabolismo , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/microbiologia , Análise de Sobrevida , Remodelação Vascular/efeitos dos fármacos
6.
Ecotoxicol Environ Saf ; 188: 109867, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31689658

RESUMO

BACKGROUND: Accumulating epidemiological studies showed that prenatal and early life exposure to ambient air pollution was important contributor to the development of childhood asthma. However, the effects and mechanisms of prenatal exposure to ozone (O3), a type of ambient air pollution, on the progression of asthma in offspring remain unclear. OBJECTIVE: This study aimed to determine the effects and mechanism of asthma in offspring after prenatal O3 exposure. METHODS: Pregnant BALB/c mice were exposed to O3 or air on gestational days (GDs) 13-18. Their offspring were sensitized and challenged to ovalbumin (OVA) to establish asthma model, and the asthma features were evaluated. The splenic natural killer (NK) cells in the offspring were measured to explore the mechanism on the effects of asthma in the offspring. The responses of the pregnant mice and dams after O3 exposure were evaluated. RESULTS: Airway inflammation, mucus secretion, OVA-specific immunoglobulin (Ig) E, T helper (Th) 2-skewed response, the frequency of CD3ε-CD49b+ splenic NK cells, the expression of tumor necrosis factor (TNF)-α, and IL (interleukin)-17 were significantly exacerbated in the OVA-induced asthma offspring after prenatal O3 exposure. In addition, airway inflammation, a lower number of CD3ε-CD49b+ splenic NK cells, and systemic oxidative stress were caused at the end of pregnancy after O3 exposure, which did not recover at the end of lactation for the first two responses. CONCLUSIONS: Prenatal O3 exposure increased the severity of OVA-induced asthma in the offspring, which might be directly induced by CD3ε-CD49b+ splenic NK cells in the offspring and indirectly related to the damaged maternal immune system.


Assuntos
Poluentes Atmosféricos/toxicidade , Asma/induzido quimicamente , Asma/patologia , Ovalbumina , Ozônio/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Asma/imunologia , Feminino , Células Matadoras Naturais/imunologia , Masculino , Camundongos Endogâmicos BALB C , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/imunologia , Equilíbrio Th1-Th2
7.
Int J Mol Sci ; 20(23)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801288

RESUMO

Human endogenous retroviruses (HERVs) are genetic elements resulting from relics of ancestral infection of germline cells, now recognized as cofactors in the etiology of several complex diseases. Here we present a review of findings supporting the role of the abnormal HERVs activity in neurodevelopmental disorders. The derailment of brain development underlies numerous neuropsychiatric conditions, likely starting during prenatal life and carrying on during subsequent maturation of the brain. Autism spectrum disorders, attention deficit hyperactivity disorders, and schizophrenia are neurodevelopmental disorders that arise clinically during early childhood or adolescence, currently attributed to the interplay among genetic vulnerability, environmental risk factors, and maternal immune activation. The role of HERVs in human embryogenesis, their intrinsic responsiveness to external stimuli, and the interaction with the immune system support the involvement of HERVs in the derailed neurodevelopmental process. Although definitive proofs that HERVs are involved in neurobehavioral alterations are still lacking, both preclinical models and human studies indicate that the abnormal expression of ERVs could represent a neurodevelopmental disorders-associated biological trait in affected individuals and their parents.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/virologia , Transtorno do Espectro Autista/virologia , Encéfalo/virologia , Retrovirus Endógenos/genética , Efeitos Tardios da Exposição Pré-Natal/virologia , Esquizofrenia/virologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/patologia , Encéfalo/imunologia , Encéfalo/patologia , Criança , Embrião de Mamíferos , Desenvolvimento Embrionário/genética , Desenvolvimento Embrionário/imunologia , Retrovirus Endógenos/patogenicidade , Exposição Ambiental/efeitos adversos , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Imunidade Inata , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Esquizofrenia/genética , Esquizofrenia/metabolismo , Esquizofrenia/patologia
8.
J Neuroinflammation ; 16(1): 226, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31733653

RESUMO

BACKGROUND: Chemerin is highly expressed in the serum, placenta tissue, and umbilical cord blood of diabetic mother; however, the impact of chemerin on cognitive disorders of offspring from mothers with diabetes in pregnancy remains unclear. METHODS: A diabetic phenotype in pregnant mice dams was induced by streptozocin (STZ) injection or intraperitoneal injection of chemerin. Behavioral changes in offspring of diabetic dams and nondiabetic controls were assessed, and changes in chemerin, two receptors of chemerin [chemerin receptor 23 (ChemR23) and chemokine (C-C motif) receptor-like 2 (CCRL2)], macrophages, and neurons in the brain tissue were studied to reveal the underlying mechanism of the behavioral changes. RESULTS: Chemerin treatment mimicked the STZ-induced symptom of maternal diabetes in mice along with the altered behavior of offspring in the open field test (OFT) assay. In the exploring process for potential mechanism, the brain tissues of offspring from chemerin-treated dams were observed with an increase level of macrophage infiltration and a decrease number of neuron cells. Moreover, an increased level of NOD-like receptor family pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like (Asc) protein as well as pyroptosis [characterized by increased active caspase-1 content and secretion of cytokines such as interleukin (IL) 1 beta (IL-1ß) and IL-18] more activated in macrophages is also observed in the brain of these diabetic dam's offspring, in the presence of ChemR23. In vitro, it was found that pyroptosis activation was increased in macrophages separated from the abdominal cavity of normal mice, after chemerin treatment. However, depletion of CCRL2 decreased the level of chemerin in the brain tissues of diabetic dams' offspring; depletion of ChemR23 decreased macrophage pyroptosis, and depletion of either receptor reversed chemerin-mediated neurodevelopmental deficits and cognitive impairment of offspring of diabetic pregnant dams. CONCLUSIONS: Chemerin induced diabetic pregnant disease and CCRL2 were required to enrich chemerin in the brain of offspring. Aggregation of chemerin could lead to macrophage recruitment, activation of pyroptosis, the release of inflammatory cytokines, a decrease in the number of neurons, and cognitive impairment in offspring in a ChemR23-dependent manner. Targeting CCRL2 and/or ChemR23 could be useful for treating neuropsychological deficits in offspring of dams with diabetes in pregnancy.


Assuntos
Encéfalo/patologia , Quimiocinas/farmacologia , Transtornos Cognitivos/etiologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Macrófagos/patologia , Efeitos Tardios da Exposição Pré-Natal , Animais , Encéfalo/metabolismo , Quimiocinas/metabolismo , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Diabetes Mellitus Experimental , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos , Gravidez , Complicações na Gravidez/etiologia , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Piroptose/fisiologia , Receptores CCR/metabolismo
9.
Asian Pac J Cancer Prev ; 20(11): 3251-3258, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759346

RESUMO

BACKGROUND: This research studied the relationship between maternal exposure to polychlorinated biphenyls and neonatal birth weight through systematic review and meta-analysis of existing literature. METHODS: We searched for all the studies published in MEDLINE / PUBMEDN / EMBASE (Medical Abstract Database) by June 2018, and seven studies had been selected. RESULTS: The results showed that there was significant correlation between birth weight reduction and PCBS exposure throughout pregnancy (ß=-0.586g, 95%CI:-0.629,-0.543). There was a negative correlation between birth weight and PCBs exposure and umbilical cord serum (ß=-0.833g) and maternal serum (ß= -0.504g).Subgroup analyses showed significantly different effects of PCBs exposure on birth weight in different regions, stages of pregnancy and study designs. It was thought the heterogeneity was mainly caused by geographical regions, stages of pregnancy, and the assessment methods. CONCLUSION: The meta analysis revealed a negative correlation between PCBs exposure and birth weight but there was significant difference in the correlation between birth weight loss.


Assuntos
Poluentes Ambientais/toxicidade , Recém-Nascido de Baixo Peso , Exposição Materna , Bifenilos Policlorados/toxicidade , Efeitos Tardios da Exposição Pré-Natal/etiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Prognóstico
10.
PLoS One ; 14(10): e0223685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600325

RESUMO

Recent research shows that preschool children born to opioid-dependent mothers are at increased risk for cognitive, psychomotor, attention, and social-emotional adjustment problems. But very little is known about their school-age functioning, particularly their educational achievement. This analysis examined the educational outcomes of a regional cohort of 100 prenatally methadone-exposed children who were prospectively studied from birth to age 9.5 years alongside a comparison group of 110 randomly identified non-exposed children born between 2003 and 2008. At age 9.5, as part of a comprehensive neurodevelopmental evaluation, children's teachers rated their achievement across the school curriculum, and children completed the Woodcock Johnson-III Tests of Achievement (WJ-III). Detailed information about the birth mother's social background, pregnancy substance use, and mental health was also collected during pregnancy/at term. Infant clinical data were collected after birth. Methadone-exposed children performed less well than non-exposed children across seven school curriculum areas rated by teachers (ps ≤.001), performed less well than non-exposed children on all reading and mathematics subtests of the WJ-III, and had higher rates of any educational delay on the WJ-III (57% vs. 15%), OR = 7.47 (3.71-15.02). Results were similar when children with severe intellectual impairment were excluded. After adjusting for confounding factors, methadone-exposed children had increased odds of educational delay, but this was only marginally significant (OR = 3.62, [1.01-13.01], p = .049). Maternal educational attainment level (OR = 0.69, [0.50-0.89], p = .006), and maternal benzodiazepine use during pregnancy (OR = 2.70 [1.03-7.12], p = .044) were also associated with later educational risk. Findings suggest that children born to opioid-dependent women enrolled in methadone maintenance are at high risk of educational delay by age 9.5 years. Children's academic difficulties appeared to reflect the effects of both adverse prenatal exposures and postnatal social risk.


Assuntos
Logro , Escolaridade , Metadona/efeitos adversos , Mães , Efeitos Tardios da Exposição Pré-Natal/patologia , Criança , Feminino , Humanos , Modelos Logísticos , Masculino , Matemática , Gravidez , Leitura , Caracteres Sexuais
11.
Am J Physiol Endocrinol Metab ; 317(6): E1094-E1107, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638854

RESUMO

Clinical and animal studies have reported an association between low birth weight and the development of nonalcoholic fatty liver disease (NAFLD) in offspring. Using a model of prenatal maternal 70% food restriction diet (FR30) in the rat, we previously showed that maternal undernutrition predisposes offspring to altered lipid metabolism in adipose tissue, especially on a high-fat (HF) diet. Here, using microarray-based expression profiling combined with metabolic, endocrine, biochemical, histological, and lipidomic approaches, we assessed whether FR30 procedure sensitizes adult male offspring to impaired lipid metabolism in the liver. No obvious differences were noted in the concentrations of triglycerides, cholesterol, and bile acids in the liver of 4-mo-old FR30 rats whichever postweaning diet was used. However, several clues suggest that offspring's lipid metabolism and steatosis are modified by maternal undernutrition. First, lipid composition was changed (i.e., higher total saturated fatty acids and lower elaidic acid) in the liver, whereas larger triglyceride droplets were observed in hepatocytes of undernourished rats. Second, FR30 offspring exhibited long-term impact on hepatic gene expression and lipid metabolism pathways on a chow diet. Although the transcriptome profile was globally modified by maternal undernutrition, cholesterol and bile acid biosynthesis pathways appear to be key targets, indicating that FR30 animals were predisposed to impaired hepatic cholesterol metabolism. Third, the FR30 protocol markedly modifies hepatic gene transcription profiles in undernourished offspring in response to postweaning HF. Overall, FR30 offspring may exhibit impaired metabolic flexibility, which does not enable them to properly cope with postweaning nutritional challenges influencing the development of nonalcoholic fatty liver.


Assuntos
Fígado Gorduroso/genética , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Desnutrição , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Feminino , Perfilação da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Gotículas Lipídicas/patologia , Fígado/patologia , Masculino , Ácidos Oleicos/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Fenômenos Fisiológicos da Nutrição Pré-Natal/genética , Ratos , Triglicerídeos/metabolismo
12.
PLoS One ; 14(9): e0221686, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31479481

RESUMO

Maternal undernutrition is known to reduce glomerular number but it may also affect tubulointerstitium, capillary density, and response to oxidative stress. To investigate whether the latter elements are affected, we examined the response to unilateral ureteral obstruction (UUO), an established model of renal tubulointerstitial fibrosis, in the kidney of offspring from control and nutrient restricted rats. Six-week old male offspring from rats given food ad libitum (CON) and those subjected to 50% food restriction throughout pregnancy (NR) were subjected to UUO for 7 days. Body weight was significantly lower in NR. Systolic blood pressure and blood urea nitrogen increased similarly in CON and NR after UUO. Tubular necrosis in the obstructed kidney, on the other hand, was more extensive in NR. Also, the collagen area, a marker of fibrosis, of the obstructed kidney was significantly increased compared with the contralateral kidney only in NR. Capillary density was decreased similarly in the obstructed kidney of CON and NR compared with the contralateral kidney. Urine nitrate/nitrite, a marker of nitric oxide production, from the obstructed kidney was significantly increased in NR compared with CON. Nitrotyrosine, a marker of nitric oxide-mediated free radical injury, was increased in the obstructed kidney compared with the contralateral kidney in both CON and NR, but the extent was significantly greater in NR. In conclusion, more severe tubular necrosis and fibrosis after UUO was observed in NR, which was thought to be due to increased nitrosative stress.


Assuntos
Necrose Tubular Aguda/etiologia , Desnutrição/complicações , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Obstrução Ureteral/complicações , Animais , Modelos Animais de Doenças , Feminino , Fibrose , Rim/patologia , Rim/fisiopatologia , Necrose Tubular Aguda/patologia , Necrose Tubular Aguda/fisiopatologia , Masculino , Troca Materno-Fetal , Nitratos/urina , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Nitritos/urina , Estresse Oxidativo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Tirosina/análogos & derivados , Tirosina/metabolismo
13.
Ecotoxicol Environ Saf ; 184: 109579, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31505405

RESUMO

DNA methylation have been suggested as possible mediators of long-term health effects of environmental stressors. This study aimed to evaluate the potential therapy of methylation of S-adenosyl-l-methionine (SAM) on PFOS induced trangeneral reproductive toxicity. In this study, postnatal 5d Sprague Dawley rats were randomly divided into four groups: control, PFOS, PFOS + SAM, and PFOS + Decitabine (DAC). The F0 rats were exposed to 5 mg/kg PFOS and SAM or DAC until PND60. The development of the offsprings were monitored without PFOS exposure. The fertility in F0, F1 rats, and change in F1 testes were observed. The results were as follows. The significant increase in F0 pregnancy rate, and survival rate in F1 offspring in PFOS + SAM relative to PFOS group were observed. Changes of birth weights and physical development in F1 offspring with SAM were approached as a corresponding variation of the control after the deparation period. No pregnant in F1 maternal rats in the PFOS and DAC groups were found, but pregnant in the SAM group. Significantly decrease in the percentage of abnormal seminiferous tubules and increase in expression of promyelocytic leukemia zinc finger (PLZF+) spermatogonial stem cells in F1 testis compared with the PFOS group. Taken together, Methyl donor SAM improve PLZF + spermatogonia stem cell proliferation, attenuate damage in testicular tissue structure, which subsequently improve the transgenerational growth retard and infertility induced by PFOS chronic stress.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Fluorcarbonetos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Reprodução/efeitos dos fármacos , S-Adenosilmetionina/uso terapêutico , Animais , Peso ao Nascer , Decitabina/uso terapêutico , Feminino , Masculino , Gravidez , Taxa de Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/mortalidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos Sprague-Dawley , Espermatogônias/citologia , Espermatogônias/efeitos dos fármacos , Taxa de Sobrevida , Testículo/citologia , Testículo/efeitos dos fármacos
14.
Acta Histochem ; 121(7): 841-851, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31431301

RESUMO

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disease characterized by defect in verbal and nonverbal communications. As, the cerebellum has the greatest number of neurons and synapses in the central nervous system so, the cerebellum has emerged as one of the target brain areas affected in autism. The aim of this work was to study the biochemical, immunohistochemical and ultrastructural characteristics of autism and the possible neuroprotective role of grape seed extract. In this study 28 male pups were divided into Control groups; Group I (saline), Group II (GSE 400 mg/kg), Group III (VPA 500 mg/kg) and Group IV (VPA and GSE). Cerebellar hemispheres were dissected out and prepared to determine the oxidative stress markers, histological, immunohistochemical and morphometric study were done. A significant elevation in oxidative stress markers in off spring of VPA treated rats in comparison to control group was detected. A significant decrease in the Purkinje cell count and nuclear size were observed. Numerous shrunken cells with hyperchromatic nuclei and ultrastructural degeneration of cytoplasmic organelles were detected. A significant rise in the area percentage of GFAP-positive immune stained cells in comparison to that of the control groups was seen. Strikingly, GSE revealed significant improvement in the oxidative stress markers and then the histological and morphometric picture of the cerebellum. GSE has neuroprotective effect on the cerebellum of VPA treated rats through its potent antioxidant effect.


Assuntos
Transtorno Autístico , Córtex Cerebelar , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Sementes/química , Ácido Valproico/efeitos adversos , Vitis/química , Animais , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Transtorno Autístico/prevenção & controle , Córtex Cerebelar/metabolismo , Córtex Cerebelar/patologia , Modelos Animais de Doenças , Feminino , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Ratos , Ácido Valproico/farmacologia
15.
Commun Biol ; 2: 310, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428698

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesic drugs, such as acetaminophen (APAP), are frequently taken during pregnancy, even in combination. However, they can favour genital malformations in newborn boys and reproductive disorders in adults. Conversely, the consequences on postnatal ovarian development and female reproductive health after in utero exposure are unknown. Here, we found that in mice, in utero exposure to therapeutic doses of the APAP-ibuprofen combination during sex determination led to delayed meiosis entry and progression in female F1 embryonic germ cells. Consequently, follicular activation was reduced in postnatal ovaries through the AKT/FOXO3 pathway, leading in F2 animals to subfertility, accelerated ovarian aging with abnormal corpus luteum persistence, due to decreased apoptosis and increased AKT-mediated luteal cell survival. Our study suggests that administration of these drugs during the critical period of sex determination could lead in humans to adverse effects that might be passed to the offspring.


Assuntos
Acetaminofen/efeitos adversos , Envelhecimento/fisiologia , Ibuprofeno/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Reprodução/fisiologia , Animais , Animais Recém-Nascidos , Proliferação de Células/efeitos dos fármacos , Feminino , Fertilidade , Proteína Forkhead Box O3/metabolismo , Células Germinativas/efeitos dos fármacos , Células Germinativas/patologia , Luteólise , Camundongos , Ovário/embriologia , Ovário/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
16.
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
17.
Dis Model Mech ; 12(8)2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31308048

RESUMO

Alongside the obesity epidemic, the prevalence of maternal diabetes is rising worldwide, and adverse effects on fetal development and metabolic disturbances in the offspring's later life have been described. To clarify whether metabolic programming effects are due to mild maternal hyperglycemia without confounding obesity, we investigated wild-type offspring of INS C93S transgenic pigs, which are a novel genetically modified large-animal model expressing mutant insulin (INS) C93S in pancreatic ß-cells. This mutation results in impaired glucose tolerance, mild fasting hyperglycemia and insulin resistance during late pregnancy. Compared with offspring from wild-type sows, piglets from hyperglycemic mothers showed impaired glucose tolerance and insulin resistance (homeostatic model assessment of insulin resistance: +3-fold in males; +4.4-fold in females) prior to colostrum uptake. Targeted metabolomics in the fasting and insulin-stimulated state revealed distinct alterations in the plasma metabolic profile of piglets from hyperglycemic mothers. They showed increased levels of acylcarnitines, gluconeogenic precursors such as alanine, phospholipids (in particular lyso-phosphatidylcholines) and α-aminoadipic acid, a potential biomarker for type 2 diabetes. These observations indicate that mild gestational hyperglycemia can cause impaired glucose tolerance, insulin resistance and associated metabolic alterations in neonatal offspring of a large-animal model born at a developmental maturation status comparable to human babies.


Assuntos
Intolerância à Glucose/etiologia , Hiperglicemia/etiologia , Insulina/genética , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Animais Geneticamente Modificados , Animais Recém-Nascidos , Feminino , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Gravidez , Suínos
18.
Nat Commun ; 10(1): 3031, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292453

RESUMO

Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.


Assuntos
Acetatos/sangue , Feto/imunologia , Pré-Eclâmpsia/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Linfócitos T Reguladores/imunologia , Acetatos/administração & dosagem , Acetatos/imunologia , Acetatos/metabolismo , Adulto , Animais , Animais Recém-Nascidos , Estudos de Casos e Controles , Desenvolvimento Infantil , Pré-Escolar , Suplementos Nutricionais , Feminino , Feto/citologia , Feto/diagnóstico por imagem , Microbioma Gastrointestinal/imunologia , Vida Livre de Germes/imunologia , Humanos , Tolerância Imunológica/imunologia , Lactente , Recém-Nascido , Estudos Longitudinais , Troca Materno-Fetal/imunologia , Camundongos , Tamanho do Órgão/imunologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Estudos Prospectivos , Timo/citologia , Timo/diagnóstico por imagem , Timo/crescimento & desenvolvimento , Timo/imunologia , Fatores de Transcrição/imunologia , Fatores de Transcrição/metabolismo , Ultrassonografia Pré-Natal , Adulto Jovem
19.
Ann N Y Acad Sci ; 1452(1): 65-77, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31317551

RESUMO

Maternal smoking during pregnancy is a significant risk factor of renal pathology in the offspring. E-cigarettes are perceived to be a safe option and are increasingly used by pregnant women either continuously during pregnancy or as a replacement for tobacco cigarettes. This study aimed to determine the effects of replacing tobacco cigarettes with e-cigarettes during pregnancy, and continuous e-cigarette use during pregnancy on the offspring's kidneys. Female Balb/c mice were exposed to either air (sham) or tobacco cigarette smoke (SE) for 6 weeks prior to mating, during gestation and lactation. A subset of the "SE group" received e-cigarette vapor (containing nicotine) after mating until pups weaned. Additional female mice were continuously exposed to e-vapor (either with or without nicotine) for 6 weeks prior to mating until pups weaned. Kidneys and urine from the male offspring were assessed at postnatal day 1, day 20 (weaning), and 13 weeks of age (adulthood). E-cigarette replacement was less detrimental to renal development and albuminuria than continuous SE during pregnancy. However, continuous e-vapor exposure during pregnancy increased markers of oxidative stress, inflammation, and fibrosis in the adult offspring, independent of nicotine. E-cigarette use during pregnancy confers future risk to the offspring's kidneys.


Assuntos
Vapor do Cigarro Eletrônico/efeitos adversos , Exposição Ambiental/efeitos adversos , Rim/fisiopatologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Biomarcadores/metabolismo , Feminino , Fibrose/metabolismo , Fibrose/patologia , Fibrose/fisiopatologia , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia
20.
Physiol Rep ; 7(12): e14154, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31243892

RESUMO

We have previously demonstrated that dexamethasone administered to pregnant rats during specific times during gestation results in a reduction in glomerular number and hypertension in offspring at 2 and 6 months of age. In this study, we examined the effect of prenatal dexamethasone administered daily on days 15 and 16 of gestation in male and female offspring after 1 year of age on glomerular filtration rate. The prenatal dexamethasone male group had a higher systolic blood pressure than the vehicle male group. Females had lower systolic blood pressures than the males and prenatal dexamethasone did not affect blood pressure in female offspring. Prenatal dexamethasone resulted in a reduction in glomerular filtration rate in male but not in female rats. When corrected for body weight, the control male rats had a lower glomerular filtration rate than the control female rats. Males had greater protein excretion than females and prenatal dexamethasone increased the protein excretion only in male rats. Glomerulosclerosis was also greater in male rats than females but was not affected by prenatal dexamethasone. In summary, male rats appear to have evidence of a decline in glomerular filtration rate after 1 year of age and prenatal dexamethasone programs an accelerated decline in glomerular filtration rate in male but not in female offspring.


Assuntos
Dexametasona/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Envelhecimento/fisiologia , Albuminúria/induzido quimicamente , Animais , Pressão Sanguínea/efeitos dos fármacos , Dexametasona/toxicidade , Esquema de Medicação , Feminino , Glucocorticoides/toxicidade , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Proteinúria/induzido quimicamente , Ratos Sprague-Dawley , Fatores Sexuais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA