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1.
Sci Total Environ ; 792: 148440, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34465058

RESUMO

Previously, we systemically confirmed that prenatal caffeine exposure (PCE) could cause intrauterine growth retardation (IUGR) and adrenal steroid synthesis dysfunction in offspring rats. However, the multi-generation inheritance of adrenal dysfunction and its epigenetic mechanism has not been reported. In this study, the PCE rat model was established, part of the pregnant rats were executed on gestational day 20, while the others were delivered normally and the fetal rats were reared into adulthood. The PCE female rats of filial generation 1 (F1) were mated with wild males to produce F2 offspring, and the same way to produce F3 offspring. All the adult female rats of three generations were sacrificed for the related detection. Results showed that PCE could decrease fetal weight, increase IUGR rate, and elevate serum corticosterone level. Meanwhile, the expression of fetal adrenal GR, DNMT3a/3b, miRNA let-7c increased while those of CTCF, H19, and StAR decreased, and the total methylation rate of the H19 promoter region was enhanced. We used SW-13 cells to clarify the molecular mechanism and found that cortisol-induced in vitro changes of these indexes were consistent with those in vivo. We confirmed that high level of cortisol through activating GR, on the one hand, promoted let-7 expression and inhibited StAR expression; on the other hand, caused high methylation and low expression of H19 by down-regulating CTCF and up-regulating DNMT3a/3b, then enhanced let-7 inhibitory effect on StAR by "molecular sponge" effect. Finally, in vivo experiments showed that the adrenal steroid synthesis function and H19/let-7 axis presented the glucocorticoid-dependent changes in the adult female F1, F2, and F3. In conclusion, PCE can cause female adrenal dysfunction with matrilineal multi-generation inheritance, which is related to the programming alteration of the H19/let-7 axis. This study provides a novel perspective to explain the multi-generation inheritance of fetal-originated disease in IUGR offspring.


Assuntos
Cafeína , Efeitos Tardios da Exposição Pré-Natal , Animais , Corticosterona , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Wistar
2.
Behav Neurol ; 2021: 6301458, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336001

RESUMO

Prenatal exposure to buprenorphine renders offspring vulnerable to cerebral impairments. In this study, our data demonstrate, for the first time, that prenatal exposure to buprenorphine escalates astrocyte activation concurrent with indications of endoplasmic reticulum (ER) stress in the hippocampi of neonates, and this can be prevented by the coadministration of dextromethorphan with buprenorphine. Furthermore, dextromethorphan can inhibit the accumulation of GPR37 in the hippocampus of newborns caused by buprenorphine and is accompanied by the proapoptotic ER stress response that involves the procaspase-3/CHOP pathway. Primary astrocyte cultures derived from the neonates of the buprenorphine group also displayed aberrant ER calcium mobilization and elevated basal levels of cyclooxygenase-2 (COX-2) at 14 days in vitro while showing sensitivity to lipopolysaccharide-activated expression of COX-2. Similarly, these long-lasting defects in the hippocampus and astrocytes were abolished by dextromethorphan. Our findings suggest that prenatal exposure to buprenorphine might instigate long-lasting effects on hippocampal and astrocytic functions. The beneficial effects of prenatal coadministration of dextromethorphan might be, at least in part, attributed to its properties in attenuating astrocyte activation and hippocampal ER stress in neonates.


Assuntos
Buprenorfina , Efeitos Tardios da Exposição Pré-Natal , Apoptose , Astrócitos , Dextrometorfano/toxicidade , Estresse do Retículo Endoplasmático , Feminino , Humanos , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
3.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(3): 279-289, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34402257

RESUMO

To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. C57BL/6 pregnant mice were given drinking water containing carbaryl dimethoate glyphosate methomyl methyl parathion triadimefon aspartame sodium benzoate calcium disodium ethylene diamine tetra-acetate ethylparaben butylparaben bisphenol A and acacia gum The effects of CM exposure on pregnancy outcome, health status of dams/offspring, levels of circulating inflammatory cytokines in dams/offspring and emotional related behaviors of offspring were evaluated. CM exposure during pregnancy had no significant effect on pregnancy outcome, liver function, body weight of the dams in late pregnancy and uterine/ovarian weight after delivery, however, it led to an increase in maternal serum IFN-γ level (<0.05). CM exposure during pregnancy had no significant effect on the liver function of offspring, but increased the serum IFN-γ, prefrontal cortex IFN-γ, and TNF-α and hippocampus IFN-γ levels in the offspring(all <0.01). In addition, the offspring of CM group showed significant abnormal emotion-related (autism-like) behaviors in adulthood, especially in male offspring. Low dose CM exposure during pregnancy may induce inflammation status in dams/offspring, and lead to autism-like behaviors in offspring, indicating the potential effects of low dose CM exposure on human maternal and infant health.


Assuntos
Transtorno Autístico , Efeitos Tardios da Exposição Pré-Natal , Adulto , Animais , Transtorno Autístico/induzido quimicamente , Feminino , Humanos , Masculino , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
4.
Int J Mol Sci ; 22(15)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34361111

RESUMO

Maternal smoking is a risk factor of preterm prelabor rupture of the fetal membranes (pPROM), which is responsible for 30% of preterm births worldwide. Cigarettes induce oxidative stress and inflammation, mechanisms both implicated in fetal membranes (FM) weakening. We hypothesized that the receptor for advanced glycation end-products (RAGE) and its ligands can result in cigarette-dependent inflammation. FM explants and amniotic epithelial cells (AECs) were treated with cigarette smoke condensate (CSC), combined or not with RAGE antagonist peptide (RAP), an inhibitor of RAGE. Cell suffering was evaluated by measuring lactate dehydrogenase (LDH) medium-release. Extracellular HMGB1 (a RAGE ligand) release by amnion and choriodecidua explants were checked by western blot. NF-κB pathway induction was determined by a luciferase gene reporter assay, and inflammation was evaluated by cytokine RT-qPCR and protein quantification. Gelatinase activity was assessed using a specific assay. CSC induced cell suffering and HMGB1 secretion only in the amnion, which is directly associated with a RAGE-dependent response. CSC also affected AECs by inducing inflammation (cytokine release and NFκB activation) and gelatinase activity through RAGE engagement, which was linked to an increase in extracellular matrix degradation. This RAGE dependent CSC-induced inflammation associated with an increase of gelatinase activity could explain a pathological FM weakening directly linked to pPROM.


Assuntos
Âmnio/patologia , Células Epiteliais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Fumaça/efeitos adversos , Adulto , Âmnio/efeitos dos fármacos , Âmnio/imunologia , Âmnio/metabolismo , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptor para Produtos Finais de Glicação Avançada
5.
Eur J Epidemiol ; 36(8): 861-872, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34420151

RESUMO

Human health effects of airborne lower-chlorinated polychlorinated biphenyls (LC-PCBs) are largely unexplored. Since PCBs may cross the placenta, maternal exposure could potentially have negative consequences for fetal development. We aimed to determine if exposure to airborne PCB during pregnancy was associated with adverse birth outcomes. In this cohort study, exposed women had lived in PCB contaminated apartments at least one year during the 3.6 years before conception or the entire first trimester of pregnancy. The women and their children were followed for birth outcomes in Danish health registers. Logistic regression was performed to estimate odds ratios (OR) for changes in secondary sex ratio, preterm birth, major congenital malformations, cryptorchidism, and being born small for gestational age. We performed linear regression to estimate difference in birth weight among children of exposed and unexposed mothers. All models were adjusted for maternal age, educational level, ethnicity, and calendar time. We identified 885 exposed pregnancies and 3327 unexposed pregnancies. Relative to unexposed women, exposed women had OR 0.97 (95% CI 0.82, 1.15) for secondary sex ratio, OR 1.13 (95% CI 0.76, 1.67) for preterm birth, OR 1.28 (95% CI 0.81, 2.01) for having a child with major malformations, OR 1.73 (95% CI 1.01, 2.95) for cryptorchidism and OR 1.23 (95% CI 0.88, 1.72) for giving birth to a child born small for gestational age. The difference in birth weight for children of exposed compared to unexposed women was - 32 g (95% CI-79, 14). We observed an increased risk of cryptorchidism among boys after maternal airborne LC-PCB exposure, but due to the proxy measure of exposure, inability to perform dose-response analyses, and the lack of comparable literature, larger cohort studies with direct measures of exposure are needed to investigate the safety of airborne LC-PCB exposure during pregnancy.


Assuntos
Poluentes Atmosféricos/toxicidade , Anormalidades Congênitas/etiologia , Exposição Ambiental/efeitos adversos , Crescimento/efeitos dos fármacos , Exposição Materna/efeitos adversos , Bifenilos Policlorados/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adulto , Estudos de Coortes , Anormalidades Congênitas/epidemiologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Bifenilos Policlorados/análise , Gravidez , Resultado da Gravidez , Nascimento Prematuro , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
6.
eNeuro ; 8(4)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34312305

RESUMO

Opioid drugs are increasingly being prescribed to pregnant women. Such compounds can also bind and activate opioid receptors in the fetal brain, which could lead to long-term brain and behavioral disruptions. We hypothesized that maternal treatment with oxycodone (OXY), the primary opioid at the center of the current crisis, leads to later neurobehavioral disorders and gene expression changes in the hypothalamus and hippocampus of resulting offspring. Female mice were treated daily with 5 mg OXY/kg or saline solution (control; CTL) for two weeks before breeding and then throughout gestation. Male and female offspring from both groups were tested with a battery of behavioral and metabolic tests to measure cognition, exploratory-like, anxiety-like, voluntary physical activity, and socio-communication behaviors. qPCR analyses were performed for candidate gene expression patterns in the hypothalamus and hippocampus of OXY and CTL derived offspring. Developmental exposure to OXY caused socio-communication changes that persisted from weaning through adulthood. Such offspring also showed cognitive impairments, reduced voluntary physical activity, and weighed more than CTL counterparts. In the hippocampus, prenatal exposure to OXY caused sex-dependent differences in expression of genes encoding opioid receptors and those involved in serotonin signaling. OXY exposure induced changes in neuropeptide hormone expression and the epigenetic modulator, Dnmt3a, in the hypothalamus, which could result in epigenetic changes in this brain region. The findings suggest cause for concern that consumption of OXY by pregnant mothers may result in permanent neurobehavioral changes in their offspring. Further work is needed to determine the potential underpinning epigenetic mechanisms.


Assuntos
Oxicodona , Efeitos Tardios da Exposição Pré-Natal , Animais , Ansiedade , Epigênese Genética , Feminino , Hipocampo , Hipotálamo , Masculino , Camundongos , Oxicodona/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética
7.
Environ Health Prev Med ; 26(1): 72, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253165

RESUMO

BACKGROUND: Particulate matter (PM), a major component of ambient air pollution, accounts for a substantial burden of diseases and fatality worldwide. Maternal exposure to PM during pregnancy is particularly harmful to children's health since this is a phase of rapid human growth and development. METHOD: In this review, we synthesize the scientific evidence on adverse health outcomes in children following prenatal exposure to the smallest toxic components, fine (PM2.5) and ultrafine (PM0.1) PM. We highlight the established and emerging findings from epidemiologic studies and experimental models. RESULTS: Maternal exposure to fine and ultrafine PM directly and indirectly yields numerous adverse birth outcomes and impacts on children's respiratory systems, immune status, brain development, and cardiometabolic health. The biological mechanisms underlying adverse effects include direct placental translocation of ultrafine particles, placental and systemic maternal oxidative stress and inflammation elicited by both fine and ultrafine PM, epigenetic changes, and potential endocrine effects that influence long-term health. CONCLUSION: Policies to reduce maternal exposure and health consequences in children should be a high priority. PM2.5 levels are regulated, yet it is recognized that minority and low socioeconomic status groups experience disproportionate exposures. Moreover, PM0.1 levels are not routinely measured or currently regulated. Consequently, preventive strategies that inform neighborhood/regional planning and clinical/nutritional recommendations are needed to mitigate maternal exposure and ultimately protect children's health.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Exposição Materna/efeitos adversos , Material Particulado/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Poluição do Ar/prevenção & controle , Animais , Doenças Cardiovasculares/induzido quimicamente , Saúde da Criança , Pré-Escolar , Modelos Animais de Doenças , Doenças do Sistema Endócrino/induzido quimicamente , Epigenômica , Feminino , Humanos , Doenças do Sistema Imunitário/induzido quimicamente , Lactente , Recém-Nascido , Masculino , Doenças do Sistema Nervoso/induzido quimicamente , Estresse Oxidativo , Tamanho da Partícula , Placenta , Gravidez , Resultado da Gravidez/epidemiologia , Doenças Respiratórias/induzido quimicamente , Adulto Jovem
8.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299119

RESUMO

The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, Δ9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9-THC-exposed offspring. Collectively, these findings indicate that prenatal Δ9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.


Assuntos
Dronabinol/toxicidade , Dislipidemias/patologia , Alucinógenos/toxicidade , Lipogênese , Fígado/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Animais Recém-Nascidos , Dislipidemias/induzido quimicamente , Feminino , Fígado/efeitos dos fármacos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Wistar
9.
Molecules ; 26(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209270

RESUMO

Resveratrol butyrate esters (RBE) are derivatives of resveratrol (RSV) and butyric acid and exhibit biological activity similar to that of RSV but with higher bioavailability. The aim of this study was designed as an animal experiment to explore the effects of RBE on the serum biochemistry, and fat deposits in the offspring rats exposed to bisphenol A (BPA), along with the growth and decline of gut microbiota. We constructed an animal model of perinatal Bisphenol A (BPA) exposure to observe the effects of RBE supplementation on obesity, blood lipids, and intestinal microbiota in female offspring rats. Perinatal exposure to BPA led to weight gain, lipid accumulation, high levels of blood lipids, and deterioration of intestinal microbiota in female offspring rats. RBE supplementation reduced the weight gain and lipid accumulation caused by BPA, optimised the levels of blood lipids, significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio, and increased and decreased the abundance of S24-7 and Lactobacillus, respectively. The analysis of faecal short-chain fatty acid (SCFA) levels revealed that BPA exposure increased the faecal concentration of acetate, which could be reduced via RBE supplementation. However, the faecal concentrations of propionate and butyrate were not only significantly lower than that of acetate, but also did not significantly change in response to BPA exposure or RBE supplementation. Hence, RBE can suppress BPA-induced obesity in female offspring rats, and it demonstrates excellent modulatory activity on intestinal microbiota, with potential applications in perinatological research.


Assuntos
Compostos Benzidrílicos/toxicidade , Ácido Butírico/farmacologia , Obesidade , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Resveratrol/farmacologia , Animais , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Sci Total Environ ; 794: 148643, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34198080

RESUMO

In recent years, there has been an increase in the number of problems associated with neurodevelopmental disorders in children, and there has been a growing interest in the relationship between environmental chemicals and children's health. The objective of this study was to examine whether an association exists between occupational or environmental prenatal maternal exposure to volatile organic compounds and the risk of neurodevelopmental disorders in children using Japanese translations of the Ages & Stages Questionnaires, Third Edition (J-ASQ-3). An increase in the risk of neurodevelopmental delay in 12-month-old children associated with maternal exposure to formalin or formaldehyde was identified in terms of problem-solving (odds ratio (OR): 1.76, 95% confidence interval (CI): 0.99-3.12) and personal-social skills (OR: 3.32, 95% CI: 1.46-7.55). It is not clear whether or not this tendency is reversible, and whether it is observed past 12 months of age. Further research and a preventive approach are needed.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Compostos Orgânicos Voláteis , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Japão , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Compostos Orgânicos Voláteis/toxicidade
11.
Environ Res ; 200: 111690, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34273365

RESUMO

BACKGROUND: Results from observational and experimental studies indicate that exposure to air pollutants during gestation reduces birth weight, whereas little is known on potential cardiometabolic consequences for the offspring at adulthood. OBJECTIVES: Our aim was to evaluate the long-term effects of gestational exposure to diesel engine exhaust (DE) on adult offspring phenotype in a rabbit model. METHODS: The protocol was designed to mimic human exposure in large European cities. Females rabbits were exposed to diluted (1 mg/m3) DE (exposed, n = 9) or clean air (controls, n = 7), from 3 days after mating, 2 h/d and 5 d/wk in a nose-only inhalation system throughout gestation (gestation days 3-27). After birth and weaning, 72 offspring (47 exposed and 25 controls) were raised until adulthood (7.5 months) to evaluate their cardio-metabolic status, including the monitoring of body weight and food intake, fasting biochemistry, body composition (iDXA), cardiovascular parameters and glucose tolerance. After a metabolic challenge (high fat diet in males and gestation in females), animals were euthanized for postmortem phenotyping. RESULTS: Sex-specific responses to maternal exposure were observed in adult offspring. Age-related increases in blood pressure (p = 0.058), glycaemia (p = 0.029), and perirenal fat mass (p = 0.026) as well as reductions in HDL-cholesterol (p = 0.025) and fat-to-body weight ratio (p = 0.011) were observed in exposed males, suggesting a metabolic syndrome. Almost only trends were observed in exposed females with higher triglycerides and decreased bone density compared to control females. Metabolic challenges triggered or amplified some biological responses, especially in females. CONCLUSIONS: In utero exposure to air pollution predisposed rabbit offspring to cardiometabolic disorders in a sex-specific manner.


Assuntos
Poluição do Ar , Doenças Cardiovasculares , Efeitos Tardios da Exposição Pré-Natal , Adulto , Animais , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Masculino , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Coelhos , Emissões de Veículos/toxicidade
12.
ACS Chem Neurosci ; 12(15): 2729-2748, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34297546

RESUMO

Methamphetamine (MA) can cross the placenta in pregnant women and cause placental abruption and developmental alterations in offspring. Previous studies have found prenatal MA exposure effects on the social and cognitive performance of children. Recent studies reported some alterations in structural and functional magnetic resonance imaging (MRI) of prenatal MA-exposed offspring. In this study, we aimed to investigate the effect of prenatal MA exposure on brain development using recently published structural, metabolic, and functional MRI studies. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and SCOPUS databases for articles that used each brain imaging modality in prenatal MA-exposed children. Seventeen studies were included in this study. We investigated brain imaging alterations using 17 articles with four different modalities, including structural MRI, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI). The participants' age range was from infancy to 15 years. Our findings demonstrated that prenatal MA exposure is associated with macrostructural, microstructural, metabolic, and functional deficits in both cortical and subcortical areas. However, the most affected regions were the striatum, frontal lobe, thalamus and the limbic system, and white matter (WM) fibers connecting these regions. The findings from our study might have valuable implications for targeted treatment of neurocognitive and behavioral deficits in children with prenatal MA exposure. Even so, our results should be interpreted cautiously due to the heterogeneity of the included studies in terms of study populations and methods of analysis.


Assuntos
Metanfetamina , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Metanfetamina/efeitos adversos , Neuroimagem , Placenta , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem
13.
Sci Total Environ ; 794: 148775, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34323766

RESUMO

Sodium ρ-perfluorous nonenoxybenzene sulfonate (OBS), a novel kind of perfluoroalkyl and polyfluoroalkyl compound, has been widely detected in the environment. The toxicity of OBS to living organisms has become a public concern. A growing body of research showed that maternal exposure to environmental pollutants caused intestinal and metabolic diseases that could be conserved across offspring. Here, female C57BL/6 mice were treated OBS at dietary levels of 0.0 mg/L (CON), 0.5 mg/L (OBS-L) and 5.0 mg/L (OBS-H) during the gestation and lactation periods. The results demonstrated that OBS treatment not only induced significant changes in the mucus secretion and ionic transport, but also disrupted the expression of antimicrobial peptides (AMPs) in the intestine of F0 and F1 generations. Additionally, OBS exposure altered bile acids metabolism and affected the transcriptional levels of critical genes involved in bile acids synthesis, signaling transfer, transportation and apical uptake. Together, all these results indicated that OBS exposure was perceived as a major stress by the intestinal epithelium that strongly affected the intestinal barrier function (including mucus, CFTR, AMPs, inflammation), and ultimately led to imbalance in the metabolism of bile acids (BAs). Moreover, we found that maternal OBS exposure had a more obvious toxicity effect on the male offspring in this experiment. Taken together, maternal OBS exposure during pregnancy and lactation had the intestinal and metabolism toxic effects on the dams and offspring, indicating that effects of maternal exposure on the toxicity of offspring could not be ignored.


Assuntos
Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Humanos , Intestinos , Lactação , Masculino , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Nutrientes , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Sódio
14.
Artigo em Inglês | MEDLINE | ID: mdl-34068255

RESUMO

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.


Assuntos
Transtorno do Espectro Autista , Clorpirifos , Praguicidas , Efeitos Tardios da Exposição Pré-Natal , Piretrinas , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/epidemiologia , Feminino , Humanos , Praguicidas/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
15.
Environ Res ; 200: 111386, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34087191

RESUMO

BACKGROUND: Improved understanding of how prenatal exposure to environmental mixtures influences birth weight or other adverse outcomes is essential in protecting child health. OBJECTIVE: We illustrate a novel exposure continuum mapping (ECM) framework that combines the self-organizing map (SOM) algorithm with generalized additive modeling (GAM) in order to integrate spatially-correlated learning into the study mixtures of environmental chemicals. We demonstrate our method using biomarker data on chemical mixtures collected from a diverse mother-child cohort. METHODS: We obtained biomarker concentrations for 16 prevalent endocrine disrupting chemicals (EDCs) collected in the first-trimester from a large, ethnically/racially diverse cohort of healthy pregnant women (n = 604) during 2009-2012. This included 4 organochlorine pesticides (OCPs), 4 polybrominated diphenyl ethers (PBDEs), 4 polychlorinated biphenyls (PCBs), and 4 perfluoroalkyl substances (PFAS). We applied a two-stage exposure continuum mapping (ECM) approach to investigate the combined impact of the EDCs on birth weight. First, we analyzed our EDC data with SOM in order to reduce the dimensionality of our exposure matrix into a two-dimensional grid (i.e., map) where nodes depict the types of EDC mixture profiles observed within our data. We define this map as the 'exposure continuum map', as the gridded surface reflects a continuous sequence of exposure profiles where adjacent nodes are composed of similar mixtures and profiles at more distal nodes are more distinct. Lastly, we used GAM to estimate a joint-dose response based on the coordinates of our ECM in order to capture the relationship between participant location on the ECM and infant birth weight after adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index (BMI), education, serum cotinine, total plasma lipids, and infant sex. Single chemical regression models were applied to facilitate comparison. RESULTS: We found that an ECM with 36 mixture profiles retained 70% of the total variation in the exposure data. Frequency analysis showed that the most common profiles included relatively low concentrations for most EDCs (~10%) and that profiles with relatively higher concentrations (for single or multiple EDCs) tended to be rarer (~1%) but more distinct. Estimation of a joint-dose response function revealed that lower birth weights mapped to locations where profile compositions were dominated by relatively high PBDEs and select OCPs. Higher birth weights mapped to locations where profiles consisted of higher PCBs. These findings agreed well with results from single chemical models. CONCLUSIONS: Findings from our study revealed a wide range of prenatal exposure scenarios and found that combinations exhibiting higher levels of PBDEs were associated with lower birth weight and combinations with higher levels of PCBs and PFAS were associated with increased birth weight. Our ECM approach provides a promising framework for supporting studies of other exposure mixtures.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Efeitos Tardios da Exposição Pré-Natal , Peso ao Nascer , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Feminino , Humanos , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
16.
Chemosphere ; 282: 130991, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34090006

RESUMO

Phthalates are non-persistent chemicals used in products of daily necessities. The evidence on the relationship of prenatal phthalates exposure and preterm birth remain uncertain and dimed. We Searched Cochrane, EMBASE, PubMed and Qvid Medline and selected studies according to a priori defined inclusion criteria. A total of 20 relevant studies published before March 31, 2020, were included. The main methods to detect heterogeneity and publication bias of included studies were the Q-statistic and Begg's test. Overall summary estimates indicated positive association of prenatal exposure to di(2-ethylhexyl) phthalate [number of studies (n) = 11, odds ratio (OR) = 1.1; 95% confidence interval (CI): 0.89, 1.4], diethyl phthalate [n = 11, OR = 1.1; 95% CI: 0.92, 1.3], dibutyl phthalate [n = 10, OR = 1.1; 95% CI: 0.77, 1.4], butyl benzyl phthalate [n = 10, OR = 1.0; 95% CI: 0.91, 1.2], diisobutyl phthalate [n = 9, OR = 1.1; 95% CI: 0.92, 1.3], diisononyl phthalate [n = 4, OR = 1.1; 95% CI: 0.85, 1.3], and phthalates were negatively associated with gestational age except di(2-ethylhexyl) phthalate and diisononyl phthalate. Most of them were not statistically significant. Subgroup analysis indicated that the heterogeneity was mainly found in the studies conducted in China and matrix collected at first trimester of pregnancy. Substantial heterogeneity and inconsistency of research methods may lead to inconsistent results of maternal phthalates exposure with preterm birth. We recommend a multicenter cohort study with a consistent approach to unravel the complex associations of prenatal phthalates exposure with birth outcomes.


Assuntos
Ácidos Ftálicos , Nascimento Prematuro , Efeitos Tardios da Exposição Pré-Natal , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Estudos Multicêntricos como Assunto , Ácidos Ftálicos/toxicidade , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
17.
Environ Res ; 200: 111459, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34126051

RESUMO

BACKGROUND: Bisphenol A (BPA) and its alternatives, including BPF and BPS, exhibit endocrine disruption activities. However, the effects of bisphenols on fetal growth in twins remain unclear. OBJECTIVE: To explore the associations of prenatal BPA, BPF, and BPS exposure with birth outcome differences in twins. METHODS: We recruited 289 twin pregnant women who visited the hospital for prenatal examination during the first trimester from 2013 to 2016. Urinary bisphenol levels were determined during the first, second, and third trimesters. The associations of maternal exposure to bisphenols with birth outcome differences in twins were analyzed after stratification by different trimesters. We applied the multiple informant model to estimate trimester-specific associations between urinary bisphenol concentrations and birth outcome differences in twins. RESULTS: We found low reproducibility (ICC<0.40) for maternal urinary BPA and moderate reproducibility (0.40 < ICC<0.75) for BPF and BPS. Urinary BPA concentrations were positively associated with within-pair twin birth weight difference when comparing the third vs. the first tertile in each of the three trimesters (i.e., 133.06 g, 95% CI: 68.19, 197.94; 144.5 g, 95%CI: 81.82-207.18 g; and 135.04 g, 95%CI: 71.37-198.71 g for the 1st, 2nd, and 3rd trimester, respectively). The effect of urinary BPA concentration on increased birth length difference within-pair twins were also observed across different trimesters (All P for trends < 0.05). Urinary BPA levels were positively associated with the within-pair birth weight and birth length differences across pregnancy trimesters (All of Type 3 P for values < 0.05). CONCLUSION: Maternal BPA exposure appeared to influence birth wight and birth length differences in twins. Our results warrant further confirmation.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Compostos Benzidrílicos/toxicidade , Estudos de Coortes , Feminino , Humanos , Exposição Materna/efeitos adversos , Fenóis , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Reprodutibilidade dos Testes
18.
Dtsch Arztebl Int ; 118(18): 313-319, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-34140080

RESUMO

BACKGROUND: In Germany, the 12-month prevalence of methamphetamine use among persons aged 15 to 34 is 1.9%. An increasing number of newborns are being born after a prenatal methamphetamine exposure (PME). In 2014, in the German state of Saxony, approximately four out of 1000 newborns were affected. METHODS: This systematic review (Prospero registration number CRD42017060536) includes publications that were published between January 1990 and November 2019. The purpose was to determine the effects of PME on the peri- and neonatal condition of the affected children and on their further long-term development. Observational studies with a control group were included in the review and examined for their methodological quality. RESULTS: 31 publications, which dealt with two prospective and six retrospective cohort studies, were included in the review. The studies involved a total of 4446 mother-child pairs with PME, compared with 43 778 pairs without PME. A metaanalysis revealed that PME was associated with, among other findings, lower birth weight (SMD = -0.348; 95% confidence interval [-0.777; 0.081]), shorter body length (SMD= -0.198 [-0.348; -0.047]), and smaller head circumference (SMD= -0.479 [-1.047; 0.089]). Some differences between the groups with and without PME persist into the toddler years. Moreover, children with PME much more commonly display psychological and neurocognitive abnormalities, which are more severe in children growing up in problematic surroundings (discord, violence, poverty, low educational level of the parent or caregiver). A limitation of this review is that not all studies employed an objective or quantitative measure of methamphet - amine use. CONCLUSION: The documented effects of PME on child development necessitate early treatment of the affected expectant mothers, children, and families. Emphasis should be placed on structured and interdisciplinary preventive measures for methamphetamine use.


Assuntos
Metanfetamina , Efeitos Tardios da Exposição Pré-Natal , Desenvolvimento Infantil , Feminino , Alemanha/epidemiologia , Humanos , Recém-Nascido , Metanfetamina/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos
19.
FASEB J ; 35(7): e21702, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34153130

RESUMO

Perinatal smoke/nicotine exposure alters lung development and causes asthma in exposed offspring, transmitted transgenerationally. The mechanism underlying the transgenerational inheritance of perinatal smoke/nicotine-induced asthma remains unknown, but germline epigenetic modulations may play a role. Using a well-established rat model of perinatal nicotine-induced asthma, we determined the DNA methylation pattern of spermatozoa of F1 rats exposed perinatally to nicotine in F0 gestation. To identify differentially methylated regions (DMRs), reduced representation bisulfite sequencing was performed on spermatozoa of F1 litters. The top regulated gene body and promoter DMRs were tested for lung gene expression levels, and key proteins involved in lung development and repair were determined. The overall CpG methylation in F1 sperms across gene bodies, promoters, 5'-UTRs, exons, introns, and 3'-UTRs was not affected by nicotine exposure. However, the methylation levels were different between the different genomic regions. Eighty one CpG sites, 16 gene bodies, and 3 promoter regions were differentially methylated. Gene enrichment analysis of DMRs revealed pathways involved in oxidative stress, nicotine response, alveolar and brain development, and cellular signaling. Among the DMRs, Dio1 and Nmu were the most hypermethylated and hypomethylated genes, respectively. Gene expression analysis showed that the mRNA expression and DNA methylation were incongruous. Key proteins involved in lung development and repair were significantly different (FDR < 0.05) between the nicotine and placebo-treated groups. Our data show that DNA methylation is remodeled in offspring spermatozoa upon perinatal nicotine exposure. These epigenetic alterations may play a role in transgenerational inheritance of perinatal smoke/nicotine induced asthma.


Assuntos
Metilação de DNA , Epigênese Genética , Pulmão/patologia , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Espermatozoides/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-Dawley , Espermatozoides/patologia
20.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067838

RESUMO

Resveratrol can affect the physiology or biochemistry of offspring in the maternal-fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4-8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p < 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut-liver axis in the offspring.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Hepatopatias/prevenção & controle , Fenóis/efeitos adversos , Resveratrol/farmacologia , Animais , Antioxidantes/metabolismo , Compostos Benzidrílicos/farmacologia , Butiratos/metabolismo , Ésteres/metabolismo , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Masculino , Fenóis/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Resveratrol/análogos & derivados
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