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1.
Rev Environ Contam Toxicol ; 251: 131-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31129734

RESUMO

Maternal exposure to endocrine-disrupting chemicals (EDCs) is associated with long-term hormone-dependent effects that are sometimes not revealed until maturity, middle age, or adulthood. The aim of this study was to conduct descriptive reviews on animal experimental and human epidemiological evidence of the adverse health effects of in utero and lactational exposure to selected EDCs on the first generation and subsequent generation of the exposed offspring. PubMed, Web of Science, and Toxline databases were searched for relevant human and experimental animal studies on 29 October 29 2018. Search results were screened for relevance, and studies that met the inclusion criteria were evaluated and qualitative data extracted for analysis. The search yielded 73 relevant human and 113 animal studies. Results from studies show that in utero and lactational exposure to EDCs is associated with impairment of reproductive, immunologic, metabolic, neurobehavioral, and growth physiology of the exposed offspring up to the fourth generation without additional exposure. Little convergence is seen between animal experiments and human studies in terms of the reported adverse health effects which might be associated with methodologic challenges across the studies. Based on the available animal and human evidence, in utero and lactational exposure to EDCs is detrimental to the offspring. However, more human studies are necessary to clarify the toxicological and pathophysiological mechanisms underlying these effects.


Assuntos
Disruptores Endócrinos , Exposição Materna/estatística & dados numéricos , Animais , Feminino , Humanos , Gravidez
2.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 11(5): 1272-1277, out.-dez. 2019.
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1022701

RESUMO

Objective: The study's purpose has been to know the viewpoint of women crack users in regards to their motherhood experience. Methods: This qualitative study was carried out with five women who used crack during pregnancy. Data was collected from May to August 2014, through the participant observation, production of field diary and semi-structured interviews. The analysis process followed the Clifford Geertz Interpretivism. Results: The crack use is not a fundamental factor in the maternity process of women who do use it. Some factors may influence the relationship between mother and child, and also the women's experience during this process, such as the desire to be a mother, pregnancy planning and family context. Conclusion: It is imperative to think of intersectoral public health policies aiming to support the crack users in an integral manner, then reducing social inequality and proposing an approach that highlights the user possibilities, as well as the individual specificity and singularity


Objetivo: Conhecer a visão da mulher usuária de crack em relação a experiência da maternidade. Método: estudo qualitativo, com cinco mulheres que utilizaram crack na gestação. Dados coletados entre maio e agosto de 2014, através da observação participante, construção de diário de campo e entrevistas semiestruturadas. A análise seguiu o Interpretativismo, de Clifford Geertz. Resultados: o uso de crack não é fator fundamental no processo de maternidade das mulheres usuárias, alguns fatores podem influenciar na relação entre mãe e filho e na experiência da mulher neste processo, como o desejo de ser mãe, planejamento da gravidez e contexto familiar. Conclusão: deve-se pensar em políticas públicas de saúde intersetoriais, visando atender as usuárias de forma integral, diminuindo a desigualdade social e propondo uma abordagem que destaque as possibilidades, especificidade e singularidade do indivíduo


Objetivo: Conocer la visión de la mujer usuaria de crack en relación a la experiencia de maternidad. Método: estudio cualitativo, con cinco mujeres que utilizaron crack en la gestación. Los datos fueron recolectados entre mayo y agosto de 2014, a través de observación participante, construcción de diario de campo y entrevistas semiestructuradas. El análisis siguió el Interpretativismo de Clifford Geertz. Resultados: uso de crack no es un factor fundamental en el proceso de maternidad de las mujeres usuarias. Algunos factores pueden influenciar en la relación entre madre e hijo y en la experiencia de la mujer en este proceso, como lo deseo de ser madre, planeamiento del embarazo y contexto familiar. Conclusión: se debe pensar en políticas públicas de salud intersectoriales, visando atender a las usuarias de forma integral, reduciendo a la desigualdad social y proponiendo un abordaje que destaque las posibilidades, especificidad y singularidad del individuo


Assuntos
Humanos , Feminino , Gravidez , Exposição Materna , Relações Materno-Fetais/psicologia , Fumar Cocaína/psicologia , Vulnerabilidade Social , Relações Familiares/psicologia , Usuários de Drogas/psicologia
3.
Bratisl Lek Listy ; 120(9): 703-710, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475559

RESUMO

OBJECTIVES:  The aim of our study was to describe the effect of prenatal testosterone exposure on 2D:4D in both sexes, and to determine whether this effect is mediated via the androgen receptor. In addition, the sex differences in lengths of 2D, 4D, and 2D:4D ratio were analyzed. BACKGROUND:  Clinical studies suggest a negative correlation between prenatal testosterone exposure and ratio of the lengths of the second and fourth digits (2D:4D). However, less is known about the underlying molecular mechanisms. METHODS:  Pregnant rats were treated with olive oil, testosterone, flutamide or testosterone with flutamide daily from the fourteenth day of pregnancy until delivery. The finger lengths of adult offspring were measured using both, digital scanning of the paws and µCT analysis of the phalanges. RESULTS:  None of the aforementioned methods revealed any effect of testosterone on 2D:4D. µCT measurements showed that prenatal hyperandrogenism in both sexes leads to shorter 2D compared to controls. Moreover, the testosterone treatment in males resulted in the shortening of 4D when compared to controls. CONCLUSION:  Prenatal hyperandrogenism leads to shorter lengths of 2D and 4D; however, it does not affect 2D:4D ratio. Whether other steroid hormones and/or testosterone metabolites affect the 2D:4D ratio requires further investigation (Tab. 5, Fig. 3, Ref. 32).


Assuntos
Exposição Materna , Testosterona , Dedos do Pé/anatomia & histologia , Animais , Feminino , Masculino , Gravidez , Ratos , Comportamento Sexual
4.
Sci Total Environ ; 692: 1106-1115, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539942

RESUMO

The aim of this study was to investigate levels of polybrominated diphenyl ethers (PBDEs) in breast milk samples from healthy primiparous mothers who had lived in Kampala capital city (urban area) and Nakaseke district (a rural area) for the last five years. Fifty samples were collected between March and June 2018 and were extracted by dispersive solid-phase extraction (SPE). Clean-up was performed on an SPE column and analysis was done using gas chromatography-mass spectrometry. Total (∑) PBDEs (BDE 28, 47, 49, 66, 77, 99, 100,138,153, 154, 183 and 209) ranged from 0.59 to 8.11 ng/g lipid weight (lw). The levels of PBDEs in samples from Kampala capital city were significantly higher than those from Nakaseke (p < 0.01, Mann-Whitney U test). The most dominant congeners were BDE-209 and -47 (contributed 37.1% and 20.2%, respectively to ∑PBDEs), suggesting recent exposure of mothers to deca-and penta-BDE formulations. Fish and egg consumption, plastics/e-waste recycling and paint fumes were associated with higher levels of BDE-47, -153 and -99, respectively, implying that diet and occupation were possible sources of the pollutants. Estimated dietary intakes (ng kg-1 body weight day-1) for BDE-47, -99 and -153 were below the US EPA reference doses for neurodevelopmental toxicity, suggesting minimal health risks to nursing infants who feed on the milk. Generally, the risk quotients for BDE-47, -99 and -153 were <1 in majority (96%) samples, indicating that the breast milk of mothers in Uganda was fit for human consumption.


Assuntos
Poluentes Ambientais/metabolismo , Éteres Difenil Halogenados/metabolismo , Exposição Materna , Leite Humano/metabolismo , Resíduo Eletrônico , Feminino , Humanos , Lactente , Bifenil Polibromatos , Uganda
5.
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
6.
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
7.
Sci Total Environ ; 685: 1152-1159, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390705

RESUMO

Increasing evidence supports that maternal exposure to vanadium (V) is associated with adverse birth outcomes including preterm birth and low birth weight. However, the effect of V exposure on intrauterine fetal growth and the underlying biological mechanism are still unclear. The present study includes 227 mother-infant pairs from the Shanghai Maternal-Child Pairs Cohort to assess the gender-specific effect of intrauterine V exposure on fetal growth and related cytokines. Maternal blood samples were collected to measure V concentration and biomarkers of growth. We used multiple linear regression to evaluate the gender-specific effect of prenatal V exposure on birth parameter and growth-related cytokines. Mixed-effect models were applied to assess the non-linear association between gestational V exposure and intrauterine fetal growth. Covariates adjusted in the regression models as potential confounders including maternal age, pre-pregnancy body mass index, gestational weeks, parity, socio-demographic status, etc. Results showed that prenatal V exposure was negatively associated with birth weight (ß = -64.73) in female newborns and body length (ß = -0.10) in male. During the fetal period, maternal V exposure was associated with decreased biparietal diameter (ß = -0.91), head circumference (ß = -2.96), femur length (ß = -0.72) and humerus length (ß = -0.64) in male. Trimester-specific analyses showed that serum V concentration in the second trimester was associated with significant reductions in intrauterine growth parameters. Besides, prenatal V exposure could down-regulate the expression of growth hormone (GH) in both maternal blood (ß = -0.23) and umbilical cord blood (ß = -1.66) in male fetuses, and the expression of brain derived neurotrophic factor (BDNF) in cord blood in females (ß = -0.52). Our results suggest that prenatal V exposure has a gender-specific effect on fetal growth and the second trimester may be a sensitive window. The disruption of grow-related cytokines may potentially be the biological mechanism of these effects.


Assuntos
Citocinas/metabolismo , Poluentes Ambientais/metabolismo , Exposição Materna/estatística & dados numéricos , Vanádio/metabolismo , Peso ao Nascer , Índice de Massa Corporal , China , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Nascimento Prematuro
8.
Environ Res ; 177: 108627, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421448

RESUMO

In recent years, several studies have addressed the issue of prenatal exposure to methylmercury (MeHg); however, few have actually analysed MeHg blood concentrations. Our study population included mothers and their new-borns from Slovenia (central region; N = 584) and Croatia (coastal region; N = 234). We have measurements of total Hg (THg) and MeHg in maternal hair, maternal peripheral blood, and cord blood. Cord blood Hg concentrations were low to moderate (median THg = 1.84 ng/g and MeHg = 1.69 ng/g). The proportion of THg as MeHg (%MeHg) in maternal and cord blood varied between 4% and 100% (coefficient of variation, CV = 32%) and between 8% and 100% (CV = 20%), respectively. Our data shows that variability of %MeHg was higher at lower blood THg levels. Concentrations of MeHg in maternal blood and cord blood were highly correlated (Rs = 0.943), in the case of inorganic Hg correlation was significant but weaker (Rs = 0.198). MeHg levels in maternal blood and cord blood were positively associated with seafood intake, maternal age, and negatively associated with pre-pregnancy BMI. Additionally, MeHg in maternal blood was positively associated with plasma selenium levels, and cord blood MeHg was negatively associated with parity. The results of multiple linear regression models showed that speciation analysis provides more defined estimation of prenatal exposure in association modelling. Associations between Hg exposure and cognitive performance of children (assessed using Bayley Scales of Infant and Toddler development) adjusted for maternal or child Apolipoprotein E genotypes showed higher model R2 and lower p-values when adjusted for MeHg compared to THg. This study demonstrates that Hg speciation improves the association between exposure and possible negative health effects.


Assuntos
Exposição Materna , Mercúrio/sangue , Compostos de Metilmercúrio/sangue , Croácia , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Gravidez , Eslovênia
9.
Sci Total Environ ; 689: 1329-1335, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31466169

RESUMO

BACKGROUND: Studies on the effects of extreme ambient temperature on the risk of adverse birth outcomes are limited, and the results are inconsistent. In this study, we evaluated the short-term effects of daily mean temperature on the risk of premature rupture of membranes (PROM) in Xinxiang, China. METHODS: Daily hospitalization data for PROM, daily meteorological data, and ambient pollution data in Xinxiang from January 1, 2015 to December 31, 2017 were collected. A quasi-Poisson generalized additive model (GAM) combined with a distributed lag non-linear model (DLNM) was applied to assess the short-term impact of temperature on PROM. The model was adjusted for relative humidity, air pollution, time trend, day of the week, and public holidays. RESULTS: The number of daily hospitalizations for PROM during the study period was 3255. With a reference median temperature of 17 °C, there were significant associations between the temperature deviation from the threshold temperature (2 °C, 12th percentile; 29 °C, 91st percentile) and PROM hospitalization at lag 0-2 days. Exposure to extreme cold (-2 °C, 1st percentile) or extreme heat (32 °C, 99th percentile) were associated with 0.528 (95% confidence interval [CI]: 0.278-0.986) and 2.161 (95% CI: 1.240-3.764) increased risks of PROM, respectively. Younger mothers with age <35 years were more sensitive to the impact of extreme temperature. CONCLUSIONS: These findings suggest that heat temperature is associated with higher PROM risk, while cold temperature might be a protective factor against PROM in Xinxiang, China. Given the adverse consequences of PROM and concerns over global climate change, pregnant women should take special precautions in summer when there are sudden increases in temperature.


Assuntos
Calor Extremo , Ruptura Prematura de Membranas Fetais/epidemiologia , Exposição Materna/estatística & dados numéricos , Adulto , China/epidemiologia , Feminino , Humanos , Gravidez , Temperatura Ambiente
10.
Environ Monit Assess ; 191(8): 500, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31321551

RESUMO

The placenta plays an important role in mediating the effect of maternal metal exposure on fetal development, acting as both barrier and transporter. Term-placenta metal levels serve as an informative snapshot of maternal/fetal exposure during pregnancy and could be used to predict offspring short- and long-term health outcomes. Here, we measured term-placenta metal levels of 11 metals in 42 placentas from the Soweto First 1000 days cohort (S1000, Soweto-Johannesburg, SA). We compared these placental metal concentrations with previously reported global cohort measurements to determine whether this cohort is at increased risk of exposure. Placental metals were tested for correlations to understand potential interactions between metals. Since these samples are from a birth cohort study, we also performed exploratory analyses to determine whether metal levels were associated with placenta and birth outcomes. Most S1000 placental metal levels were similar to other cohorts; however, cadmium (Cd) levels up to 50-fold lower, and essential elements nickel (Ni) and chromium (Cr) level up to 6- and 16-fold lower, respectively. Cd, Se, and Ni were associated with placenta and birth outcomes. Studies are ongoing to examine underlying mechanisms and how these developmental differences affect long-term health.


Assuntos
Monitoramento Ambiental/métodos , Exposição Materna , Metais Pesados/análise , Placenta/química , Oligoelementos/análise , Estudos de Coortes , Feminino , Humanos , Masculino , Gravidez , Resultado da Gravidez , África do Sul
11.
Sci Total Environ ; 690: 388-399, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299572

RESUMO

In this study we reconstruct the long-term exposure of Czech mothers to polychlorinated biphenyls (PCBs) and determine the causes of high contamination of breast milk by indicator PCBs (iPCBs). A data set containing information from more than 1000 primiparous women from the Czech Republic was used, including iPCB concentrations in breast milk, individual physiology and living characteristics. The time series of PCB intakes for the whole period from the beginning of PCB production in 1958 until 2011 were reconstructed. We estimated the individual lifetime exposure of mothers for all iPCBs, i.e. congeners 28, 52, 101, 118, 138, 153 and 180, using a physiologically based pharmacokinetic (PBPK) model. Various model scenarios were investigated to determine the influence of physiology, age at delivery, past dietary exposure, and food composition on concentrations in breast milk for all iPCBs. The highest contributions to the presence of iPCBs in breast milk were observed for food composition. The main factor determining the concentration of higher-chlorinated PCBs (138, 153 and 180) was past exposure. The most important parameter for identification of children's postnatal exposure through breast milk was the time-span from the maximum of the exposure peak to the birth of the child. The current concentrations of iPCBs in breast milk in the Czech population are still high because the maximum of the exposure peak occurred more than 10 years later than in other European countries and was very broad, e.g. covered more than 10 years.


Assuntos
Poluentes Ambientais/metabolismo , Exposição Materna/estatística & dados numéricos , Bifenilos Policlorados/metabolismo , Adulto , República Tcheca , Exposição Dietética/estatística & dados numéricos , Feminino , Humanos , Leite Humano
12.
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
13.
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
14.
Toxicol Lett ; 314: 18-26, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299270

RESUMO

Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the potential intrauterine programming mechanism. During pregnancy, rats were divided into a PNE group and a control group. After birth, rats were given a high-fat diet for 6 months and long-distance running for 6 weeks. The rats were euthanized at 18 months after birth (PM18) and on gestational day 20 (GD20), respectively. Knee joints were collected for histochemistry, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Histological analyses and the Mankin's score showed increased cartilage destruction and accelerated OA progression in adult offspring from the PNE group. Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFß) signaling pathway. Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. Traced back to the intrauterine period, it was found that the number of chondrocytes and the contents of Col2A1 and aggrecan in the matrix in the PNE group were decreased. And, the expression of the TGFß signaling pathway was inhibited. These results suggested that PNE enhanced the susceptibility of OA in male elderly offspring rats by down-regulating TGFß signaling, which increased articular cartilage local inflammation, matrix degradation, and cell apoptosis. This study confirmed the developmental origin of OA, and clarified the congenital and the living environment impact on the occurrence and development of OA. Our findings provide a theoretical and experimental basis for OA early prevention.


Assuntos
Articulações/efeitos dos fármacos , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Osteoartrite/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fatores Etários , Agrecanas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Condrogênese/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Feminino , Idade Gestacional , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Articulações/metabolismo , Articulações/patologia , Masculino , Exposição Materna , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Gravidez , Ratos Wistar , Fatores de Risco , Fatores Sexuais
15.
Toxicol Lett ; 314: 63-74, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31306741

RESUMO

This study aimed to verify the toxic effects of prenatal caffeine exposure (PCE) on the podocyte development in male offspring, and to explore the underlying intrauterine programming mechanisms. The pregnant rats were administered with caffeine (30 to 120 mg/kg⋅d) during gestational day (GD) 9 to 20. The male fetus on GD20 and the offspring at postnatal week (PW) 6 and PW28 were sacrificed. The results indicated that PCE caused ultrastructural abnormalities on podocyte, and inhibited the expression of podocyte marker genes such as Nephrin, Wilms tumor 1 (WT1), the histone 3 lysine 9 acetylation (H3K9ac) level in the Kruppel-like factor 4 (KLF4) promoter and its expression in the male offspring from GD20 to PW28. Meanwhile, the expression of glucocorticoid receptor (GR) and histone deacetylase 7 (HDAC7) in the fetus were increased by PCE. In vitro, corticosterone increased GR and HDAC7 whereas reduced the H3K9ac level of KLF4 and KLF4/Nephrin expression. KLF4 over-expression reversed the reduction of Nephrin expression, knockdown of HDAC7 and GR antagonist RU486 partially reversed the inhibitory effects of corticosterone on H3K9ac level and KLF4 expression. In conclusion, PCE caused podocyte developmental toxicity in male offspring, which was associated with corticosterone-induced low-functional programming of KLF4 through GR/HDAC7/H3K9ac pathway.


Assuntos
Cafeína/toxicidade , Estimulantes do Sistema Nervoso Central/toxicidade , Histonas/metabolismo , Nefropatias/induzido quimicamente , Fatores de Transcrição Kruppel-Like/metabolismo , Podócitos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Acetilação , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Idade Gestacional , Glucocorticoides/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Nefropatias/embriologia , Nefropatias/genética , Nefropatias/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Lisina , Masculino , Exposição Materna , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fenótipo , Podócitos/metabolismo , Podócitos/ultraestrutura , Gravidez , Regiões Promotoras Genéticas , Ratos Wistar , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Environ Pollut ; 253: 909-917, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351299

RESUMO

Tetrabromobisphenol A (TBBPA) is a nonregulated brominated flame retardant with a high production volume, and it is applied in a wide variety of consumer products. TBBPA is ubiquitous in abiotic matrices, wildlife and humans around the world. This paper critically reviews the published scientific data concerning the disposition, metabolism or kinetics and toxicity of TBBPA in animals and humans. TBBPA is rapidly absorbed and widely distributed among tissues, and is excreted primarily in the feces. In rats, TBBPA and its metabolites have limited systemic bioavailability. TBBPA has been detected in human milk in the general population. It is available to both the developing fetus and the nursing pups following maternal exposure. It has been suggested that TBBPA causes acute toxicity, endocrine disruptor activity, immunotoxicity, neurotoxicity, nephrotoxicity, and hepatotoxicity in animals. Cell-based assays have shown that TBBPA can induce reactive oxygen species in a concentration-dependent manner, and it promotes the production of inflammatory factors such as TNF α, IL-6, and IL-8. Cells exposed to high levels of TBBPA exhibit seriously injured mitochondria and a dilated smooth endoplasmic reticulum. This review will enhance the understanding of the potential risks of TBBPA exposure to ecological and human health.


Assuntos
Retardadores de Chama/toxicidade , Bifenil Polibromatos/toxicidade , Animais , Animais Selvagens , Disponibilidade Biológica , Fezes , Feminino , Retardadores de Chama/metabolismo , Halogenação , Humanos , Cinética , Masculino , Exposição Materna , Ratos
17.
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
18.
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
19.
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
20.
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
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