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Exogenous melatonin protects preimplantation embryo development from decabromodiphenyl ethane-induced circadian rhythm disorder and endogenous melatonin reduction
2022
Shi, Feifei | Qiu, Jinyu | Zhang, Shaozhi | Zhao, Xin | Feng, Daofu | Feng, Xizeng
Decabromodiphenyl ethane (DBDPE) is a novel flame retardant that is widely used in plastics, electronic products, building materials and textiles. Our previous studies have revealed the oocyte toxicity of DBDPE, but the effect of DBDPE on preimplantation embryo development has not been reported. Here, we investigated whether and how DBDPE exposure affects preimplantation embryo development. Adult female mice were orally exposed to DBDPE (0, 5, 50, 500 μg/kg bw/day) for 14 days. First, we found that after DBDPE exposure, mice showed obvious circadian rhythm disorder. Moreover, the development of preimplantation embryos was inhibited in DBDPE-exposed mice after pregnancy. Then, we further explored and revealed that DBDPE exposure reduced the endogenous melatonin (MLT) level during pregnancy, thereby inhibiting the development of preimplantation embryos. Furthermore, we discovered that exogenous MLT supplementation (15 mg/kg bw/day) rescued the inhibition of preimplantation embryo development induced by DBDPE, and a mechanistic study demonstrated that exogenous MLT inhibited the overexpression of ROS and DNA methylation at the 5-position of cytosine (5-mC) in DBDPE-exposed preimplantation embryos. Simultaneously, MLT ameliorated the DBDPE-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential (MMP), ATP, and Trp1 expression. Additionally, MLT restored DBDPE-induced changes in zona pellucida (ZP) hardness and trophectoderm (TE) cortical tension. Finally, the protective effect of MLT on embryos ameliorated the adverse reproductive outcomes (dead fetus, fetus with abnormal liver, fetal weight loss) induced by DBDPE. Collectively, DBDPE induced preimplantation embryo damage leading to adverse reproductive outcomes, and MLT has emerged as a potential tool to rescue adverse reproductive outcomes induced by DBDPE.
Afficher plus [+] Moins [-]Relationship between thyroid hormone parameters and exposure to a mixture of organochlorine pesticides, mercury and nutrients in the cord blood of newborns
2022
Wang, Ju | Cao, Lu-Lu | Gao, Zhen-Yan | Zhang, Hong | Liu, Jun-Xia | Wang, S. S. (Su Su) | Pan, Hui | Yan, Chong-Huai
The fetus is prenatally exposed to a mixture of organochlorine pesticides (OCPs), mercury (Hg), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and selenium (Se) through maternal seafood consumption in real-life scenario. Prenatal exposure to these contaminants and nutrients has been suggested to affect thyroid hormone (TH) status in newborns, but the potential relationships between them are unclear and the joint effects of the mixture are seldom analyzed. The aim of the study is to investigate the associations of prenatal exposure to a mixture of OCPs, Hg, DHA, EPA and Se with TH parameters in newborns. 228 mother-infant pairs in Shanghai, China were included. We measured 20 OCPs, total Hg, DHA, EPA and Se in cord blood samples as exposure variables. The total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels and the FT3/FT4 ratio in cord serum were determined as outcomes. Using linear regression models, generalized additive models and Bayesian kernel machine regression, we found dose-response relationships of the mixture component with outcomes: among the contaminants, p,p'-DDE was the most important positive predictor of TT3, while HCB was predominantly positively associated with FT3 and the FT3/FT4 ratio, indicating different mechanisms underlying these relationships; among the nutrients, EPA was first found to be positively related to the FT3/FT4 ratio. Additionally, we found suggestive evidence of interactions between p,p'-DDE and HCB on both TT3 and FT3, and EPA by HCB interactions for TT3, FT3 and FT3/FT4 ratio. However, the overall effects of the mixture on thyroid hormone parameters were not significant. Our result suggests that prenatal exposure to p,p’-DDE, HCB and EPA as part of a mixture might affect thyroid function of newborns in independent and interactive ways. The potential biological mechanisms merit further investigation.
Afficher plus [+] Moins [-]Gestational PCB52 exposure induces hepatotoxicity and intestinal injury by activating inflammation in dam and offspring mice: A maternal and progeny study
2022
Xu, Ling-Ling | Zhang, Qin-Yao | Chen, Yu-Kui | Chen, Li-Jian | Zhang, Kai-Kai | Wang, Qi | Xie, Xiao-Li
Although Polychlorinated biphenyl (PCB) levels are decreased in the environment, the adverse effects of gestational exposure on the mother and offspring cannot be ignored due to the vulnerability of the fetus. In the present study, pregnant Balb/c mice were administered PCB52 (1 mg/kg BW/day) or corn oil vehicle by gavage until parturition. In the dams, PCB52 caused histopathological changes in the liver, higher serum levels of aminotransferase and alanine aminotransferase, and activated apoptosis and autophagy, suggesting hepatotoxicity. Overexpressed indicators of TLR4 pathway were observed in the liver of PCB52-exposed dams, indicated hepatic inflammation. Moreover, PCB52 exposure weakened the intestinal barrier and triggered inflammatory response, which might contribute to the hepatic inflammation by gut-liver axis. In the pups, prenatal PCB52 exposure affected the sex ratio at birth and reduced birth length and weights. Similar to the dams, prenatal PCB52 exposure induced hepatotoxicity in the pups without gender difference. Consistent with the alteration of gut microbiota, intestinal inflammation was confirmed, accompanying the disruption in the intestinal barrier and the activation of apoptosis and autophagy in the PCB52-exposed pups. Intestinal injury might be responsible for hepatotoxicity at least in part. Taken together, these findings suggested that gestational PCB52 exposure induced hepatic and intestinal injury in both maternal and offspring mice by arousing inflammation.
Afficher plus [+] Moins [-]Dermal uptake: An important pathway of human exposure to perfluoroalkyl substances?
2022
Ragnarsdóttir, Oddný | Abdallah, Mohamed Abou-Elwafa | Harrad, Stuart
Per- and polyfluoroalkyl substances (PFAS) have been produced and used in a broad range of products since the 1950s. This class, comprising of thousands of chemicals, have been used in many different products ranging from firefighting foam to personal care products and clothes. Even at relatively low levels of exposure, PFAS have been linked to various health effects in humans such as lower birth weight, increased serum cholesterol levels, and reduced antibody response to vaccination. Human biomonitoring data demonstrates ubiquitous exposure to PFAS across all age groups. This has been attributed to PFAS-contaminated water and dietary intake, as well as inadvertent ingestion of indoor dust for adults and toddlers. In utero exposure and breast milk have been indicated as important exposure pathways for foetuses and nursing infants. More recently, PFAS have been identified in a wide range of products, many of which come in contact with skin (e.g., cosmetics and fabrics). Despite this, few studies have evaluated dermal uptake as a possible route for human exposure and little is known about the dermal absorption potential of different PFAS. This article critically investigates the current state-of-knowledge on human exposure to PFAS, highlighting the lack of dermal exposure data. Additionally, the different approaches for dermal uptake assessment studies are discussed and the available literature on human dermal absorption of PFAS is critically reviewed and compared to other halogenated contaminants, e.g., brominated flame retardants and its implications for dermal exposure to PFAS. Finally, the urgent need for dermal permeation and uptake studies for a wide range of PFAS and their precursors is highlighted and recommendations for future research to advance the current understanding of human dermal exposure to PFAS are discussed.
Afficher plus [+] Moins [-]Exposure to acrylamide induces cardiac developmental toxicity in zebrafish during cardiogenesis
2018
Huang, Mengmeng | Jiao, Jingjing | Wang, Jun | Xia, Zhidan | Zhang, Yu
Acrylamide (AA), an environmental pollutant, has been linked to neurotoxicity, genotoxicity and carcinogenicity. AA is widely used to synthesize polymers for industrial applications, is widely found in Western-style carbohydrate-rich foods and cigarette smoke, and can also be detected in human umbilical cord blood and breast milk. This is the first study that demonstrated the cardiac developmental toxicity of AA in zebrafish embryos. Post-fertilization exposure to AA caused a clearly deficient cardiovascular system with a shrunken heart and abortive morphogenesis and function. Disordered expression of the cardiac genes, myl7, vmhc, myh6, bmp4, tbx2b and notch1b, as well as reduced number of myocardial cells and endocardial cells, indicated the collapsed development of ventricle and atrium and failed differentiation of atrioventricular canal (AVC). Although cell apoptosis was not affected, the capacity of cardiomyocyte proliferation was significantly reduced by AA exposure after fertilization. Further investigation showed that treatment with AA specifically reduced the expressions of nkx2.5, myl7 and vmhc in the anterior lateral plate mesoderm (ALPM) during the early cardiogenesis. In addition, AA exposure disturbed the restricted expressions of bmp4, tbx2b and notch1b during atrioventricular (AV) valve development and cardiac chambers maturation. Our results showed that AA-induced cardiotoxicity was related to decreased cardiac progenitor genes expression, reduced myocardium growth, abnormal cardiac chambers morphogenesis and disordered AVC differentiation. Our study demonstrates that AA exposure during a time point analogous to the first trimester in humans has a detrimental effect on early heart development in zebrafish. A high ingestion rate of AA-containing products may be an underlying risk factor for cardiogenesis in fetuses.
Afficher plus [+] Moins [-]Does maternal environmental tobacco smoke interact with social-demographics and environmental factors on congenital heart defects?
2018
Liu, Xiaoqing | Nie, Zhiqiang | Chen, Jimei | Guo, Xiaoling | Ou, Yanqiu | Chen, Guanchun | Mai, Jinzhuang | Gong, Wei | Wu, Yong | Gao, Xiangmin | Qu, Yanji | Bell, Erin M. | Lin, Shao | Zhuang, Jian
Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004–2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25–1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD association on the multiplicative scale. These findings may help to identify high-risk populations for CHD, providing an opportunity for targeted preventive interventions.
Afficher plus [+] Moins [-]Characterization of ambient carbon monoxide and PM 2.5 effects on fetus development, liver enzymes and TSH in Isfahan City, central Iran
2021
Nourouzi, Zohreh | Chamani, Atefeh
Ambient carbon monoxide (CO) and particulate matters (PMs) are two important air pollutants in urban areas with known impacts on fetuses. Hence, this study measured some biochemistry factors of 200 neonates with birth dates from January 19 to October 12, 2020, including the birth weight and height and the serum levels of ALT, AST, ALP, GGT, and TSH. The Support Vector Machine-fitted land-use regression approach was used to predict the spatio-temporal variability of intra-urban PM 2.5 and CO concentrations by month during the pregnancy period of the cases employing 5 variables of Digital Elevation Model (DEM), slope, and distance from Compressed Natural Gas (CNG) stations, Bus Rapid Transit (BRT) stations, and mines and industries. Spearman correlation analysis (p < 0.05) was performed between the neonate indices and mean monthly PM 2.5 and CO concentrations at the exact residential address of maternal cases and their nearby areas in 250, 500, 1000, 1500, and 2000 m-radius buffer rings. All modeling efforts succeeded in predicting CO and PM 2.5 levels with acceptable adjusted r² values. Northern Isfahan had relatively higher CO and PM 2.5 concentrations due to its adjacency to low-vegetated open lands and its high traffic load as compared to southern areas. The correlation results between the neonate biochemistry indices and mean PM 2.5 and CO concentrations were mostly positive in most buffer rings, especially in the >500 m-radius buffer rings for PM 2.5 and in the 2000 m-radius rings for CO. Although the correlation results of PM 2.5 followed a detectable trend in the buffer rings, the associations between CO and the neonate biochemistry indices differed significantly between the buffer rings. Results showed that increasing mean monthly concentration of CO and PM 2.5 may stimulate further production of liver enzymes while decreasing the birth weight and height.
Afficher plus [+] Moins [-]In-utero exposure to HT-2 toxin affects meiotic progression and early oogenesis in foetal oocytes by increasing oxidative stress
2021
Hong, Yi | Mu, Xinyi | Ji, Xingduo | Chen, Xuemei | Geng, Yanqing | Zhang, Yan | Liu, Qiqi | Li, Fangfang | Wang, Yingxiong | He, Junlin
HT-2 toxin (HT-2), a mycotoxin produced by Fusarium species, is detected in a variety of cereal grain-based human food and animal feed. Apart from its well-established immunotoxicity and haematotoxicity, it also causes reproductive disorders. In the present study, we revealed the adverse effects of HT-2 on early oogenesis at the foetal stage. Pregnant mice were orally administered with HT-2 for 3 days at mid-gestation. Oocytes from female foetuses exposed to HT-2 displayed defects in meiotic prophase, including unrepaired DNA damage, elevated recombination levels, and reduced expression of meiotic-related genes. Subsequently, increased oxidative stress was observed in the foetal ovaries exposed to HT-2, along with the elevated levels of reactive oxygen species, malondialdehyde, catalase, and superoxide dismutase 1/2, thereby resulting in impaired mitochondrial membrane potential and cell apoptosis. Furthermore, pre-treatment with urolithin A, a natural compound with antioxidant activities, partially reversed the delayed meiotic process by alleviating oxidative stress. Since early oogenesis is essential to determine female fertility in adult life, this study indicated that brief maternal exposure to HT-2 toxin may compromise the fertility of a developing female foetus.
Afficher plus [+] Moins [-]Prenatal exposure levels of polybrominated diphenyl ethers in mother-infant pairs and their transplacental transfer characteristics in Uganda (East Africa)
2020
Matovu, Henry | Ssebugere, Patrick | Sillanpää, Mika
Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants with adverse effects on the foetus and infants. This study aimed at assessing in utero exposure levels and transplacental transfer (TPT) characteristics of BDE congeners in primiparous mothers from Kampala, the capital city of Uganda. Paired human samples (30 placenta and 30 cord blood samples) were collected between April and June 2018; and analysed for a suite of 24 tri-to deca-BDE congeners. Extraction was carried out using liquid-liquid extraction and sonication for cord blood and placenta samples, respectively. Clean-up was done on a solid phase (SPE) column and analysis was performed using gas chromatography/mass spectrometry (GC/MS). Total (∑) PBDEs were 0.25–30.9 ng/g lipid weight (lw) (median; 7.11 ng/g lw) in placental tissues and 1.65–34.5 ng/g lw (median; 11.9 ng/g lw) in cord blood serum, with a mean difference of 1.26 ng/g lw between the compartments. Statistical analysis showed no significant difference between the levels of PBDEs in cord blood and placenta samples (Wilcoxon signed rank test, p = 0.665), possibly because foetus and neonates have poorly developed systems to metabolise the pollutants from the mothers. BDE-209 was the dominant congener in both matrices (contributed 40.5% and 51.2% to ∑PBDEs in placenta and cord blood, respectively), suggesting recent and on-going maternal exposure to deca-BDE formulation. Non-significant associations were observed between ∑PBDEs in maternal placenta and maternal age, household income, pre-pregnancy body mass index (BMI), and beef/fish consumption. This suggested on-going exposure to PBDEs through multiple sources such as dust from indoor/outdoor environments and, ingestion of other foods. Based on absolute concentrations, the extent of transplacental transport was greater for higher congeners (BDE-209, -206 and −207) than for lower ones (such as BDE-47), suggesting alternative TPT mechanisms besides passive diffusion. More studies with bigger sample sizes are required to confirm these findings.
Afficher plus [+] Moins [-]Tetrabromobisphenol A: Disposition, kinetics and toxicity in animals and humans
2019
Yu, Yunjiang | Yu, Ziling | Chen, Haibo | Han, Yajing | Xiang, Mingdeng | Chen, Xichao | Ma, Ruixue | Wang, Zheng-Dong
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.
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