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1.
Adv Exp Med Biol ; 1155: 801-819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468449

RESUMO

Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance. By increasing chloride concentration through GABA-ARs, taurine serves as an effective inhibitory compound for maintaining appropriate levels of brain excitability. Considering this pharmacological mechanism of taurine facilitated inhibition through the GABA-AR, the present pilot study sought to explore the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random assignments to either solutions of Saline, Taurine, or Taurine Derived compounds (i.e., TD-101, TD-102, or TD-103) to assess the rats' responsiveness to each drug in mitigating the developmental Pb2+-exposure through the GABAergic system. Long Evans Hooded rats were assessed using an Open Field (OF) test for preliminary locomotor assessment. Approximately 24-h after the OF, the same rats were exposed to the Elevated Plus Maze (EPM) and were given an i.p. injection of 43 mg/Kg of the Saline, Taurine, or TD drugs 15-min prior to testing. Each rat was tested using the random assignment method for each pharmacological condition, which was conducted using a triple-blind procedure. The OF data revealed that locomotor activity was unaffected by Pb2+-exposure with no gender differences observed. However, Pb2+-exposure induced an anxiogenic response in the EPM, which interestingly, was ameliorated in a gender-specific manner in response to taurine and TD drugs. Female rats exhibited more anxiogenic behavior than the male rats; and as such, exhibited a greater degree of anxiety that were recovered in response to Taurine and its derivatives as a drug therapy. The results from the present psychopharmacological pilot study suggests that Taurine and its derivatives could provide useful data for further exploring the pharmacological mechanisms and actions of Taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for treating anxiety and other associated mood disorders.


Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Chumbo/efeitos adversos , Exposição Materna/efeitos adversos , Taurina/farmacologia , Animais , Feminino , Masculino , Projetos Piloto , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Distribuição Aleatória , Ratos , Ratos Long-Evans
2.
Adv Exp Med Biol ; 1155: 821-846, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468450

RESUMO

Lead (Pb2+) is a developmental neurotoxicant that causes lifelong cognitive dysfunctions. In particular, Pb2+-induced frontoexecutive dysfunctions emerge later in life when the cortex is fully myelinated, thereby permitting the ability to assess the extent to which Pb2+ has developmentally impacted higher order cognitive and behavioral systems. The present study evaluated the effects of developmental Pb2+-exposure (150 ppm lead acetate in the drinking water) in Long Evans Hooded rats through the Attention Set-Shift Test (ASST) between postnatal days (PND) 60-90. Treatment groups were comprised of Control (0 ppm), Perinatal (150 ppm), and Perinatal+Taurine (150 ppm + 0.05% Taurine in the drinking water) rats (N = 36; n = 6 per treatment group for each sex). Frontoexecutive functions were evaluated based on trials-to-criterion (TTC) and errors-to-criterion (ETC) measures for simple and complex discriminations (SD & CD), intradimensional and extradimensional shifts (ID & ED), as well as reversals (Rev) of the CD, I-, and ED stages, respectively. Post-testing, the prelimbic (PrL), infralimbic (IL), orbital ventral frontal (OV), orbital ventro-lateral (OVL), and hippocampal (HP) brain regions were extracted and processed through Liquid Chromatography/Mass Spectrophotometry (LC/MS) for determining the GABA and Taurine ratios relative to Glutamate, Dopamine, Norepinephrine, Epinephrine, and Serotonin. The ASST data revealed that Perinatal rats are negatively impacted by developmental Pb2+-exposures evidenced by increased TTC and ETC to learn the SD, ID, and ID-Rev with unique sex-based differences in frontoexecutive dysfunctions. Moreover, Perinatal+Taurine co-treated rats exhibited a recovery of the frontoexecutive dysfunctions observed in Perinatal rats to levels equivalent to Control rats across both sexes. The LC/MS data revealed altered brain sub-region specific patterns across the PrL, IL, OV, OVL, and HP in response to developmental Pb2+-exposure that produced an altered neurochemical signaling profile in a sex-dependent manner, which may underlie the observed frontoexecutive dysfunctions, cognitive inflexibility, and associated motivation deficits. When taurine co-treatment was administered concurrently for the duration of developmental Pb2+-exposure, the observed frontoexecutive dysfunctions were significantly reduced in both ASST task performance and neurochemical ratios that were comparable to Control levels for both sexes. Altogether, the data suggest that taurine co-treatment may facilitate neuroprotection, mitigate neurotransmitter excitability balancing, and perhaps ameliorate against neurotoxicant exposures in early development as a potential psychopharmacotherapy.


Assuntos
Atenção , Função Executiva , Chumbo/efeitos adversos , Exposição Materna/efeitos adversos , Taurina/farmacologia , Animais , Feminino , Aprendizagem , Masculino , Fármacos Neuroprotetores/farmacologia , Gravidez , Ratos , Ratos Long-Evans
3.
Toxicol Lett ; 314: 98-105, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31348986

RESUMO

Parental exposure to cigarette smoke is closely related to the development of long-term metabolic diseases in the offspring. However, different exposure times at various developmental stages may cause these effects to vary. In this study, mice were exposed to cigarette smoke condensate (CSC) during the developmental time stages of paternal puberty or/and maternal pregnancy. The results showed that either paternal or maternal exposure to CSC could lead to increased low birth weight (LBW) and fetal growth restriction (FGR) of the offspring, but maternal factors were the leading ones. Moreover, maternal exposure during pregnancy could induce lipid metabolism abnormalities in the adulthood offspring. Most importantly, additional paternal CSC exposure further induced diabetes in adolescent offspring who experienced altered weight gain, blood lipids, and glucose metabolism. A preliminary analysis indicated that the offspring with metabolic abnormalities also had significant changes in their intestinal microbiota. In conclusion, this study showed that parental CSC exposure has an impact on the metabolic properties of the offspring, and multiple parental exposures to adverse factors may significantly increase the risk of long-term metabolic abnormalities.


Assuntos
Glicemia/metabolismo , Fumar Cigarros/efeitos adversos , Diabetes Mellitus/etiologia , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Fumaça/efeitos adversos , Fatores Etários , Animais , Biomarcadores/sangue , Peso ao Nascer , Diabetes Mellitus/sangue , Feminino , Retardo do Crescimento Fetal/etiologia , Microbioma Gastrointestinal , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Gravidez , Medição de Risco , Fatores de Risco
4.
Medicine (Baltimore) ; 98(30): e16556, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348278

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) may be 1 of etiologic factors responsible for congenital heart diseases (CHDs). Variations of the microsomal epoxide hydrolase (EPHX1) gene, as well as their possible interactions with PAHs exposure, may increase susceptibility to CHDs.This case-control study investigated the risk of CHDs in relation to the EPHX1 polymorphisms and assessed the interactions between these polymorphisms and PAHs exposure in 357 mothers of CHDs fetuses and 270 control mothers. Logistic regression models for the risk of CHDs were applied to determine the effect of genetic polymorphisms using additive, recessive, and dominant genetic models, as well as gene-exposure interactions. Multiple testing was adjusted by applying the false discovery rate (FDR).None of the maternal genetic polymorphisms of EPHX1 was associated with CHDs occurrence. Only the single nucleotide polymorphism rs1051740 was associated with an increased risk of right-sided obstructive malformations under the recessive model (adjusted odds ratio [aOR] = 1.852, 95% confidence interval [CI]: 1.065, 3.22) before FDR correction. A possible modifying effect of PAHs exposure on genetic polymorphisms of EPHX1 was found in susceptibility to CHDs, though no multiplicative-scale interactions between maternal exposure to PAHs and polymorphisms of EPHX1 gene were seento affect the risk of CHDs.The role of EPHX1 gene polymorphisms for CHDs need to be further evaluated, in particularly by interacting with PAHs exposure.


Assuntos
Poluentes Atmosféricos/toxicidade , Epóxido Hidrolases/genética , Cardiopatias Congênitas/genética , Exposição Materna/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adulto , Estudos de Casos e Controles , China , Feminino , Feto/metabolismo , Predisposição Genética para Doença/embriologia , Predisposição Genética para Doença/genética , Cardiopatias Congênitas/embriologia , Humanos , Modelos Logísticos , Mães , Razão de Chances , Polimorfismo de Nucleotídeo Único , Gravidez
5.
Environ Pollut ; 252(Pt A): 330-335, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158661

RESUMO

Aluminum is a widely distributed metal that has been reported to have embryotoxicity and fetotoxicity in animal studies. However, there has been no study of the association between prenatal aluminum exposure and newborn mitochondrial DNA copy number (mtDNAcn). We aimed to investigate the effect of prenatal aluminum exposure on newborn mtDNAcn. A total of 762 mother-newborn pairs were recruited between November 2013 and March 2015 in Wuhan city, China. We measured maternal urinary aluminum concentrations at three trimesters of pregnancy. Relative mtDNAcn was measured in DNA extracted from umbilical cord blood samples. We used generalized estimating equations to assess the relationship between prenatal aluminum exposure and newborn mtDNAcn. The geometric means of creatinine corrected aluminum concentrations were 31.0 µg/g Cr (95% CI: 27.6, 34.7), 40.9 µg/g Cr (95% CI: 35.7, 46.8) and 58.4 µg/g Cr (95% CI: 51.2, 67.4) for the first, second and third trimesters, respectively. After adjustment for potential confounding factors, a doubling of maternal urinary aluminum concentrations during the second and third trimesters was related to 3.16% (95% CI: 0.88, 5.49) and 4.20% (95% CI: 1.64, 6.81) increases in newborn mtDNAcn, respectively, while the association between maternal urinary aluminum concentration during the first trimester and newborn mtDNAcn was not significant (percent difference: 0.70%, 95% CI: -2.25, 3.73). Prenatal aluminum exposure during the second and third trimesters was positively associated with newborn mtDNAcn. Further studies are essential to elucidate on the potential health consequences of newborn mtDNAcn.


Assuntos
Alumínio/toxicidade , Variações do Número de Cópias de DNA/efeitos dos fármacos , DNA Mitocondrial/genética , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/genética , Adulto , Alumínio/urina , China , Cidades , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Recém-Nascido , Masculino , Mitocôndrias/genética , Gravidez , Primeiro Trimestre da Gravidez
6.
Ann Agric Environ Med ; 26(2): 266-272, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31232058

RESUMO

INTRODUCTION: In animal models, gestational exposure to inorganic arsenic has been associated with higher corticosterone concentration and consequent impairment of stress control in offspring. An equivalent association relating cortisol, a glucocorticoid hormone, in humans has not been previously studied. OBJECTIVE: The aim of the study was to explore the association between prenatal inorganic arsenic exposure and salivary cortisol in infants from Arica, Chile. MATERIAL AND METHODS: A cohort study of 168 mother-child dyads was recruited. In the 2nd trimester of pregnancy, urinary inorganic arsenic was assessed; 18-24 months after delivery, salivary cortisol was measured in the children. Maternal cortisol, maternal depression, stress, and socio-economic status were also evaluated. RESULTS: The adjusted association was estimated with multiple linear regression after evaluating confounding through a directed acyclic graph. Median urinary inorganic arsenic in pregnant women was 14.1 µg/L (IQR: 10.4-21.7) while salivary cortisol in the children was 0.17 µg/L (IQR: 0.11-0.38). Among children from the highest income families (> 614 USD/month), arsenic exposure was associated with salivary cortisol. Children in the third quartile of arsenic exposure had -0.769 units of the logarithm of salivary cortiso, compared with those in the first quartile (p = 0.045). CONCLUSIONS: In this sample, prenatal exposure to arsenic was associated with salivary cortisol (third quartile of inorganic arsenic), only in infants belonging the highest income strata (> 614 USD). More studies are needed to confirm these preliminary results.


Assuntos
Arsênico/análise , Hidrocortisona/análise , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Saliva/química , Adulto , Arsênico/urina , Criança , Pré-Escolar , Chile , Feminino , Humanos , Hidrocortisona/metabolismo , Lactente , Masculino , Gravidez , Gestantes , Estudos Prospectivos , Saliva/metabolismo , Adulto Jovem
7.
Chemosphere ; 233: 452-461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31176908

RESUMO

BACKGROUND: It has been widely reported that gestational exposure to fine particulate matters (PM2.5) is associated with a series of adverse birth outcomes. However, the discrepancy between ambient PM2.5 concentrations and personal PM2.5 exposure would significantly affect the estimation of exposure-response relationship. OBJECTIVE: Our study aimed to predict gestational personal exposure to PM2.5 from the satellite-driven ambient concentrations and analyze the influence of other potential determinants. METHOD: We collected 762 72-h personal exposure samples from a panel of 329 pregnant women in Shanghai, China as well as their time-activity patterns from Feb 2017 to Jun 2018. We established an ambient PM2.5 model based on MAIAC AOD at 1 km resolution, then used its output as a major predictor to develop a personal exposure model. RESULTS: Our ambient PM2.5 model yielded a cross-validation R2 of 0.96. Personal PM2.5 exposure levels were almost identical to the corresponding ambient concentrations. After adjusting for time-activity patterns and meteorological factors, our personal exposure has a CV R2 of 0.76. CONCLUSION: We established a prediction model for gestational personal exposure to PM2.5 from satellite-based ambient concentrations and provided a methodological reference for further epidemiological studies.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Exposição por Inalação/análise , Exposição Materna , Material Particulado/análise , China , Feminino , Humanos , Recém-Nascido de Baixo Peso , Exposição por Inalação/efeitos adversos , Aprendizado de Máquina , Exposição Materna/efeitos adversos , Valor Preditivo dos Testes , Gravidez , Nascimento Prematuro/induzido quimicamente , Prognóstico , Imagens de Satélites
8.
Life Sci ; 232: 116575, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211999

RESUMO

AIMS: Maternal smoking is considered a risk factor for childhood obesity. In a rat model of tobacco exposure during breastfeeding, we previously reported hyperphagia, overweight, increased visceral fat and hyperleptinemia in adult female offspring. Obesity and eating disorders are associated with impairment in the endocannabinoid (EC) and dopaminergic (DA) systems. Considering that women are prone to eating disorders, we hypothesize that adult female Wistar rats that were exposed to cigarette smoke (CS) during the suckling period would develop EC and DA systems deregulation, possibly explaining the eating disorder in this model. MATERIAL AND METHODS: To mimic maternal smoking, from postnatal day 3 to 21, dams and offspring were exposed to a smoking machine, 4×/day/1 h (CS group). Control animals were exposed to ambient air. Offspring were evaluated at 26 weeks of age. KEY FINDINGS: Concerning the EC system, the CS group had increased expression of diacylglycerol lipase (DAGL) in the lateral hypothalamus (LH) and decreased in the liver. In the visceral adipose tissue, the EC receptor (CB1r) was decreased. Regarding the DA system, the CS group showed higher dopamine transporter (DAT) protein expression in the prefrontal cortex (PFC) and lower DA receptor (D2r) in the arcuate nucleus (ARC). We also assessed the hypothalamic leptin signaling, which was shown to be unchanged. CS offspring showed decreased plasma 17ß-estradiol. SIGNIFICANCE: Neonatal CS exposure induces changes in some biomarkers of the EC and DA systems, which can partially explain the hyperphagia observed in female rats.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Endocanabinoides/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Animais Recém-Nascidos , Fumar Cigarros , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/efeitos dos fármacos , Neurônios Dopaminérgicos/fisiologia , Endocanabinoides/fisiologia , Feminino , Região Hipotalâmica Lateral/efeitos dos fármacos , Região Hipotalâmica Lateral/metabolismo , Hipotálamo/metabolismo , Lactação/efeitos dos fármacos , Leptina/metabolismo , Lipase Lipoproteica/efeitos dos fármacos , Exposição Materna/efeitos adversos , Obesidade/etiologia , Obesidade/metabolismo , Ratos , Ratos Wistar , Receptores de Canabinoides/efeitos dos fármacos , Fumar , Tabaco
9.
Food Chem Toxicol ; 131: 110554, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207305

RESUMO

The results of a large 2-year bisphenol A (BPA) rat study conducted by the NTP, called the CLARITY-BPA Core Study, were recently released. This study addressed some of the toxicological issues associated with BPA, including endocrine disruption and non-monotonic dose responses (NMDR). The study involved oral gavage treatment of rats to BPA at doses of 2.5-25,000 µg/kg-bw/day. To address NMDR, the 81 statistically significant findings (based on the primary statistical tests) from the Core Study were evaluated using a recently published methodology that relies upon six checkpoints to determine if there is evidence for a NMDR. Failure to meet the majority of the checkpoints indicates limited evidence of NMDR. The analysis found that only 2 of the 81 findings met at least 5 of the checkpoints: an increase in percent basophils in stop-dose females and decreased total bile acids in stop-dose males. However, these findings are not concordant or consistent with those of other BPA data. Importantly, none of the endocrine-related or reproductive endpoints fulfilled at least 5 of the checkpoints. This analysis found limited evidence for NMDR associated with BPA treatment in the study. These results are consistent with the conclusions reached in the Core Study report.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Animais , Basófilos/metabolismo , Ácidos e Sais Biliares/metabolismo , Relação Dose-Resposta a Droga , Feminino , Masculino , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley
10.
Environ Pollut ; 246: 876-884, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159137

RESUMO

Ecotoxicological studies show the association between pesticide pollution and transgenerational toxicity in aquatic organisms. However, a less considered risk is that many pesticides can be metabolized and transferred to offspring as new toxicants. In this study, we used zebrafish to evaluate the maternal transfer risk of fipronil (FIP), which is a great threat to aquatic organisms with toxic metabolite formation. After 28-day exposure to environmentally relevant concentrations (1.0, 5.0 and 10.0 µg/L) of FIP in adult female zebrafish (F0), the toxicants off-loading and transgenerational toxicity in offspring were studied. High burdens of FIP and its sulfone metabolite were found in both F0 and the embryos (F1), resulting in increased CYP450 activity. The residual levels of the metabolite were higher than those of the parent compound. Chiral analysis further showed a preferential accumulation of S-enantiomer of FIP in both F0 and F1. Maternal exposure to FIP increased the malformation rate and decreased the swim speed in larvae. Additionally, after exposure, the levels of thyroid hormones (THs), including triiodothyronine (T3) and thyroxine (T4), decreased in both generations, particularly in the F1. Gene transcription expression along the hypothalamic-pituitary-thyroid (HPT) axis was also significantly affected. Maternal exposure to FIP increased sulfone metabolite enrichment and cause multiple toxic effects in F1. Findings from this study highlight the key role of biologically active product formation in the maternal transfer of pollutants and associated risk assessment.


Assuntos
Exposição Materna/efeitos adversos , Praguicidas/toxicidade , Pirazóis/toxicidade , Sulfonas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Disruptores Endócrinos/metabolismo , Disruptores Endócrinos/toxicidade , Feminino , Praguicidas/metabolismo , Pirazóis/metabolismo , Sulfonas/metabolismo , Hormônios Tireóideos/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra
11.
BMC Public Health ; 19(1): 705, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174511

RESUMO

BACKGROUND: Air pollution is becoming an increased burden to the world. Previous studies have confirmed its effects on adverse birth outcomes, but few associated with premature small for gestational age (SGA). We report a retrospective cohort study conducted in Changzhou city to evaluate the association between air pollutants (PM2.5, SO2 and NO2) and premature SGA during pregnancy. METHODS: A total of 46,224 births were collected from January, 2013 to December, 2016, in Changzhou Maternity and Child Health Care Hospital, finally 2709 preterm births were admitted for study. Corresponding air monitoring data were collected from Changzhou Environmental Protection Agency. Generalized estimating equations were used to examine the association between these air pollutants and premature SGA controlling for individual covariates in single- and multi-pollutant models. RESULTS: We found that, in the third trimester, every 10 µg/m3 increments in PM2.5 concentration were associated with premature SGA (OR = 1.18, 95% CI: 1.03-2.83; OR = 1.37, 95% CI: 1.03-3.58) in two- and three-pollutants models. In the whole gestation, a 10 µg/m3 increment in PM2.5 concentration in two- and three-pollutant models were related to premature SGA (OR = 1.53, 95% CI: 1.38-2.47; OR = 1.73, 95% CI: 1.18-2.57). The OR (95% CI) of premature SGA were increasing across quintiles of PM2.5, SO2, NO2 concentrations during the whole gestation period adjusting for confounders (P for trend < 0.001). CONCLUSIONS: These results indicated that pregnant women exposed to PM2.5, combined with other pollutants in the third trimester have a higher risk to deliver premature SGA babies, providing further evidence linking PM2.5 and pregnancy outcomes.


Assuntos
Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Recém-Nascido Pequeno para a Idade Gestacional , Exposição Materna/efeitos adversos , Nascimento Prematuro/epidemiologia , Adulto , Poluentes Atmosféricos/análise , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Material Particulado/análise , Gravidez , Resultado da Gravidez , Nascimento Prematuro/etiologia , Estudos Retrospectivos
12.
Chemosphere ; 233: 174-182, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31173955

RESUMO

Emerging evidence suggests environmental contaminant exposures during critical windows of development may contribute to the increasing prevalence of obesity. It has been shown that early life polybrominated diphenyl ethers exposures have critical impacts on child weight trajectories, however, little is known about their maternal mechanisms responsible for offspring obesity development. In this study, we investigated the effects of perigestational low-dose 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) exposure on maternal metabolome, and its possible link to adult offspring bodyweight changes. Female Sprague-Dawley rats were exposed to daily doses of 0.1, or 1 mg/kg BDE-47 from 10 days prior to conception until offspring were weaned on postnatal day 21, and then a gas chromatography-mass spectrometry based metabolomics analysis was used to uncover the global metabolic response in dams. The pups continued to grow into adulthood for measurements of bodyweight. Perigestational BDE-47 exposure caused increased adult bodyweight in male but not in female offspring and dams. Metabolomics revealed significant changes in maternal serum metabolites that clearly distinguish BDE-47 from control rats. These differentially expressed metabolites were primarily implicated in amino acid, lipid, carbohydrate, and energy metabolisms, which was confirmed by pathway analysis. Importantly, most of these identified metabolites were decreased, a state similar to maternal malnutrition that can predispose adult male offspring to weight increase and adiposity in a postnatal environment with abundant calories. Collectively, our data suggest that perigestational exposure to low-dose BDE-47 produces altered maternal serum metabolome, which may be an additional contributing factor to weight gain in adult male offspring.


Assuntos
Peso Corporal/efeitos dos fármacos , Éteres Difenil Halogenados/toxicidade , Exposição Materna/efeitos adversos , Metaboloma/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/toxicidade , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Éteres Difenil Halogenados/administração & dosagem , Lactação , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley , Ganho de Peso/efeitos dos fármacos
13.
Environ Sci Pollut Res Int ; 26(19): 19403-19410, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31073831

RESUMO

Although BPA use is widespread and often detectable in humans, little is known about its exposure levels and potential exposure predictors in pregnant women in China. We investigated the BPA exposure levels in pregnant women and its health implications and potential exposure predictors. Urinary BPA levels were measured for 506 pregnant women in northern China. Hazard quotients (HQs) based on estimated daily intakes (EDIs) were conducted. Sociodemographic characteristics and food consumption during pregnancy were collected and seasons of sample collection were recorded. The detection rate of urinary BPA was 86.6% and the median concentrations were 0.48 µg/L (1.05 µg/g creatinine). The EDI (median = 0.008 µg/kg bw/day) was much lower than the recommended tolerable daily doses and the HQ (median = 0.002) much lower than 1. The urine collected in summer had significantly higher BPA levels than that collected in other seasons (ß = 0.225; 95% CI - 0.008, 0.458; p = 0.03). Women "always consuming shellfish" had significantly higher BPA levels than those "seldom consuming shellfish" (ß = 0.341; 95% CI 0.022, 0.66; p = 0.04). The study found a wide exposure to BPA among pregnant women in this region, which might be associated with seasonal variation and shellfish consumption. Although the HQs suggested no obvious risk, further attention to the comprehensive exposure and potential determinants should be paid in view of its endocrine-disrupting potential.


Assuntos
Compostos Benzidrílicos/urina , Exposição Dietética/efeitos adversos , Disruptores Endócrinos/urina , Exposição Materna/efeitos adversos , Fenóis/urina , Adulto , China , Estudos de Coortes , Creatinina/análise , Exposição Dietética/análise , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Medição de Risco , Alimentos Marinhos , Estações do Ano , Frutos do Mar , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
14.
Dev Neuropsychol ; 44(4): 339-356, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31059292

RESUMO

We examined the roles of maternal and child lifetime stress exposures, infant temperament (orienting/regulation, surgency/extraversion), and maternal caregiving during infancy and preschool on preschoolers' working memory and inhibitory control in a sociodemographically diverse pregnancy cohort. Working memory was predicted by infant orienting/regulation, with differential effects by the level of maternal cognitive support in infancy; maternal lifetime stress exposures exerted independent negative effects on working memory. Inhibitory control was positively associated with maternal emotionally supportive behaviors in infancy, which mediated the effects of maternal lifetime stress exposures on inhibitory control. These findings have implications for interventions designed to optimize child executive functioning.


Assuntos
Desenvolvimento Infantil , Inibição (Psicologia) , Exposição Materna/efeitos adversos , Memória de Curto Prazo , Relações Mãe-Filho/psicologia , Mães/psicologia , Orientação , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Autocontrole/psicologia , Estresse Psicológico , Temperamento , Criança , Pré-Escolar , Cognição , Função Executiva , Feminino , Seguimentos , Humanos , Lactente , Masculino , Gravidez , Estudos Prospectivos
15.
Environ Sci Pollut Res Int ; 26(20): 20137-20147, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31111384

RESUMO

Fetal growth has been demonstrated to be an important predictor of perinatal and postnatal health. Although the effects of maternal exposure to air pollution during pregnancy on fetal growth have been investigated using ultrasound in many previous studies, the results were inconsistent and disputable. We aimed to qualitatively and quantitatively investigate the associations of air pollution exposure during different periods of pregnancy with fetal growth and anthropometric measurements at birth. We searched for all studies investigating the associations of air pollution exposure during pregnancy with fetal growth and birth anthropometric measurements in English and Chinese databases published before July 31, 2017. A random-effects model was employed in the meta-analysis to estimate the pooled effects of each 10 µg/m3 increment in air pollutant exposure. The ACROBAT-NRSI tool was applied to assess the quality of each included study, and the GRADE tool was employed to assess the overall quality of the meta-analysis. Maternal PM2.5 exposure (10 µg/m3) during the entire pregnancy was negatively associated with head circumference at birth (ß = - 0.30 cm, 95% CI - 0.49, - 0.10), and NO2 exposure during the entire pregnancy was significantly linked to shorter length at birth (ß = - 0.03 cm, 95% CI - 0.05, - 0.02). Maternal exposure to higher NO2 and PM2.5 during pregnancy may impair neonatal head circumference and length development, respectively. More studies are needed to confirm the effects of NO2 and PM2.5 and to identify the sources and major toxic components of PMs.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Desenvolvimento Fetal , Exposição Materna/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estatura , Feminino , Cabeça/anatomia & histologia , Humanos , Recém-Nascido , Gravidez
16.
Environ Pollut ; 251: 699-707, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108303

RESUMO

We conducted a meta-analysis to evaluate the association between prenatal cadmium (Cd) exposure and birth weight. PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for studies published before March 2019. We used a model-based method, standardizing effect size from linear regression models to include a maximum number of studies during our quantitative evaluations. As a result, 11 articles from the general population, containing 10 birth cohorts and one cross-sectional study, were included. Our meta-analysis demonstrated that a 50% increase of maternal urine Cd (UCd) would be associated with a 6.15 g decrease in neonatal birth weight (ß = -6.15 g, 95% CI: -10.81, -1.49) as well as a 50% increase of maternal blood Cd (BCd) would be associated with an 11.57 g decrease (ß = -11.57 g; 95% CI: -18.85, -4.30). Stratified analysis of UCd data indicated that the results of female newborns were statistically significant (ß = -8.92 g, 95% CI: -17.51, -0.34), as was the first trimester (ß = -11.34 g, 95% CI: -19.54, -3.14). Furthermore, increased UCd levels were associated with a higher rate of low birth weight (LBW) risk (OR = 1.12, 95% CI: 1.03, 1.22). This meta-analysis demonstrated that elevated maternal Cd levels are associated with decreased birth weight and higher LBW risk.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Cádmio/toxicidade , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/etiologia , Cádmio/sangue , Cádmio/urina , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
17.
Chemosphere ; 230: 432-439, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31121507

RESUMO

This study was conducted to investigate the effects of maternal exposure to BPA on testicular development in offspring males. Pregnant Kunming mice were randomly divided into 7 groups with 20 mice in each group. Group A was the control group and the mice were given distilled water orally. Mice in groups B, C, D, E, F, G received BPA orally at a dose of 0.05 mg/kg/d, 0.5 mg/kg/d, 5 mg/kg/d, 10 mg/kg/d, 20 mg/kg/d, 50 mg/kg/d, respectively. F0 mice were exposed to BPA for 40 days from gestation day 0 to lactation day 21. F1 male mice were sacrificed at weaning (postnatal day 21). Histological observations revealed architectural damages in testis in BPA exposed groups. The testicular organ index increased significantly when the BPA oral exposure dose was above 20 mg/kg/d (P < 0.05). BPA contents in serum of F1 male mice increased significantly when BPA was above 5 mg/kg/d (P < 0.05), while the contents significant increased in maternal serum when BPA was higher than 0.5 mg/kg/d. The damage of cell nuclear DNA of testis was significantly aggravated when BPA was above 5 mg/kg/d. The expression of AR in the testis was significantly increased when BPA was above 20 mg/kg/d (P < 0.05). Transcriptome sequencing showed that the Snrnp 40 which encoding U5 snRNA subunit was significantly up-regulated in spliceosome pathway, and the Hnrnpu which encoding splicing universal protein component was significantly down-regulated. The blockage of spliceosome might be one of the reasons why BPA affects testicular development.


Assuntos
Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Processamento de RNA/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica , Lactação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Testículo/embriologia , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Transcriptoma/efeitos dos fármacos
18.
Environ Toxicol ; 34(7): 878-885, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037826

RESUMO

Perfluorooctanoic acid (PFOA) is an octanoic acid and is found in wildlife and humans. We have investigated mitochondrial toxicity in isolated mitochondria from, placenta, brain, liver, and heart after oral exposure with PFOA in mice during gestational days (7-15). Histopathological examination and mitochondrial toxicity parameters were assayed. Results indicated that PFOA decreased the weight of the fetus and placenta, the length of the fetus and the diameter of the placenta, dead fetuses and dead macerated fetuses in treated mice with 25 mg/kg. Histopathological examination showed that PFOA induced pathological abnormalities in liver, brain, heart, and placenta. Also, PFOA induced mitochondria toxicity in brain, liver, heart of mouse fetus. Our results indicate that PFOA up to 20 mg/kg exposure adversely affect embryofetal/developmental because for mitochondria dysfunction. These results suggested that mitochondrial dysfunction induced by PFOA in liver, heart, and brain lead to developmental toxicity and abnormality in tissues.


Assuntos
Aborto Espontâneo/induzido quimicamente , Caprilatos/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Feto/efeitos dos fármacos , Fluorcarbonetos/toxicidade , Exposição Materna/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/ultraestrutura , Feminino , Feto/metabolismo , Feto/patologia , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Masculino , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/fisiologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/fisiologia , Miocárdio/ultraestrutura , Gravidez
19.
Ecotoxicol Environ Saf ; 180: 106-113, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078017

RESUMO

Exposure to polychlorinated biphenyls (PCBs), which are persistent lipophilic environmental pollutants, has a variety of adverse effects on wildlife and human health, including bone mineralization, growth and mechanical strength. The present study evaluated the effects of lactational exposure to nondioxin-like PCB-155 and dioxin-like PCB-169, individually and in combination, on pubertal rat femur development and its biomechanics. After offspring delivery, Wistar rat mothers were divided into four groups, i.e., PCB-169, PCB-155, PCB-155+169 and control, and were administered PCBs intraperitoneally. Data on bone geometry, biomechanics and mineral composition were obtained by analysis of femurs from 42-day-old offspring by microCT scanning, three-point bending test and inductively coupled plasma mass spectrometry. Decreased somatic mass and femur size, i.e., mass, periosteal circumference and cross sectional area, were observed in the PCB-169 and PCB-155 groups. Additionally, lactational exposure to planar PCB-169 resulted in harder and more brittle bones containing higher amounts of minerals. Combined exposure to structurally and functionally different PCBs demonstrated only mild alterations in bone width and mineralization. To conclude, our results demonstrated that alterations, observed on postnatal day 42, were primarily induced by PCB-169, while toxicity from both of the individual congeners may have been reduced in the combined group.


Assuntos
Poluentes Ambientais/toxicidade , Fêmur/efeitos dos fármacos , Exposição Materna/efeitos adversos , Bifenilos Policlorados/toxicidade , Animais , Exposição Dietética/efeitos adversos , Feminino , Fêmur/química , Fêmur/crescimento & desenvolvimento , Masculino , Minerais/análise , Ratos Wistar
20.
Ecotoxicol Environ Saf ; 180: 123-129, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31082575

RESUMO

1-Nitropyrene (1-NP), a typical nitrated polycyclic aromatic hydrocarbon, is widely distributed in the environment and is well known for its mutagenic effects. Recently, we found that gestational 1-NP exposure induced fetal growth restriction. In this study, we further evaluated the effect of in utero 1-NP exposure on postnatal growth and neurobehavioral development in the offspring. Pregnant mice were administered with 1-NP (10 µg/kg) by gavage daily in late pregnancy (GD13-GD17). The body weight of each offspring was measured from PND1 to 12 weeks postpartum. Exploration and anxiety related activities were detected by open-field test at 6 weeks postpartum. Learning and memory were assessed by Morris Water Maze at 7 weeks postpartum. And depressive-like behaviors were estimated by sucrose preference test at 10 weeks postpartum. Significant body weight reduction was observed in 1-NP-exposed female offspring at PND1, PND14 and PND21 while the lower body weight was only found at PND1 for 1-NP-exposed male offspring. Exploration and anxiety activities at puberty, and depressive-like behavior in adulthood were not disturbed in offspring prenatally exposed to 1-NP. Interestingly, spatial learning and memory ability at puberty was impaired in females but not in males prenatally exposed to 1-NP. These findings suggest that gestational 1-NP exposure delays postnatal growth and impaired neurobehavioral development in a gender-dependent manner.


Assuntos
Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Mutagênicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Pirenos/toxicidade , Animais , Feminino , Masculino , Memória/efeitos dos fármacos , Camundongos Endogâmicos ICR , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Fatores Sexuais , Aprendizagem Espacial/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos
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