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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.
Show more [+] Less [-]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.
Show more [+] Less [-]Association between organohalogenated pollutants in cord blood and thyroid function in newborns and mothers from Belgian population
2018
Dufour, Patrice | Pirard, Catherine | Seghaye, Marie-Christine | Charlier, Corinne
The last decades have seen the increasing prevalence of thyroid disorders. These augmentations could be the consequence of the increasing contamination of the environment by chemicals that may disrupt the thyroid function. Indeed, in vitro studies have shown that many chemicals contaminating our environment and highlighted in human serum, are able to interfere with the thyroid function. Given the crucial importance of thyroid hormones on neurodevelopment in fetus and newborns, the influence of these pollutants on newborn thyroid homeostasis is a major health concern. Unfortunately, the overall evidence for a deleterious influence of environmental pollutants on thyroid remains poorly studied. Therefore, we assessed the contamination by polychlorinated biphenyls (PCBs), organochlorine pesticides and perfluorinated compounds (PFC) in 221 cord blood samples collected in Belgium between 2013 and 2016. Our results showed that compared to previous studies performed on newborns recruited in Belgium during the two last decades, the present pollutant contamination is declining. Multivariate statistical analyses pointed out a decrease of thyroid stimulating hormone (TSH) level in male newborns with detectable level of 4,4′- dichlorodiphenyldichloroethylene (4,4′-DDE) in comparison with those with no detectable level (p = 0.025). We also highlighted a negative association between perfluorononanoic acid (PFNA) concentration and TSH in male newborns (p = 0.018). Logistic regression showed increased odds ratio for presentation of hypothyroid in mother for each one unit augmentation of log natural concentration of PFOA (OR = 2.30, [1.18–4.5]) and PFOS (OR = 2.03 [1.08–3.83]). Our findings showed that the residual contamination by PFCs and organochlorine pollutants in cord blood are correlated with thyroid hormone in the newborns and the risk of hypothyroid in mothers.
Show more [+] Less [-]Triclosan affects axon formation in the neural development stages of zebrafish embryos (Danio rerio)
2018
Kim, Jin | Oh, Hanseul | Ryu, Bokyeong | Kim, Ukjin | Lee, Ji-min | Jung, Cho-Rok | Kim, C-yoon | Park, Jae-Hak
Triclosan (TCS) is an organic compound with a wide range of antibiotic activity and has been widely used in items ranging from hygiene products to cosmetics; however, recent studies suggest that it has several adverse effects. In particular, TCS can be passed to both fetus and infants, and while some evidence suggests in vitro neurotoxicity, there are currently few studies concerning the mechanisms of TCS-induced developmental neurotoxicity. Therefore, this study aimed to clarify the effect of TCS on neural development using zebrafish models, by analyzing the morphological changes, the alterations observed in fluorescence using HuC-GFP and Olig2-dsRED transgenic zebrafish models, and neurodevelopmental gene expression. TCS exposure decreased the body length, head size, and eye size in a concentration-dependent manner in zebrafish embryos. It increased apoptosis in the central nervous system (CNS) and particularly affected the structure of the CNS, resulting in decreased synaptic density and shortened axon length. In addition, it significantly up-regulated the expression of genes related to axon extension and synapse formation such as α1-Tubulin and Gap43, while decreasing Gfap and Mbp related to axon guidance, myelination and maintenance. Collectively, these changes indicate that exposure to TCS during neurodevelopment, especially during axonogenesis, is toxic. This is the first study to demonstrate the toxicity of TCS during neurogenesis, and suggests a possible mechanism underlying the neurotoxic effects of TCS in developing vertebrates.
Show more [+] Less [-]Effects of glyphosate on the ovarian function of pregnant mice, the secretion of hormones and the sex ratio of their fetuses
2018
Ren, Xin | Li, Ruonan | Liu, Junze | Huang, Kai | Wu, Sheng | Li, Yansen | Li, Chunmei
Glyphosate is the active ingredient of the commercial formulation Roundup®, which is used worldwide. This study aimed to investigate the toxic effects of pure glyphosate or Roundup® on pregnant mice and their fetuses during pregnancy. From gestation days (GDs) 1–19, ICR mice were orally administered distilled water, 0.5% glyphosate solution or 0.5%-glyphosate Roundup® solution. The ovaries and serum were collected at GD19. The results showed decreases in body weight gain and, ovary and liver weight in glyphosate-treated mice. Additionally, histopathological alterations in the ovary including increased atretic follicles, interstitial fibrosis and decreased mature follicles were observed in the groups treated with glyphosate. The serum concentrations of both progesterone and estrogen were markedly altered after glyphosate exposure, and there were also changes in the expression of GnRH, LHR, FSHR, 3β-HSD and Cyp19a1 genes at the hypothalamic-pituitary-ovarian axis. Furthermore, oxidative stress was observed in the treated mice, increasing the activity of T-AOC, CAT and GSH-Px, as well as the MDA content in both the serum and ovary. With regard to litters, the sex ratio was significantly altered by pure glyphosate. These results show that glyphosate is able to cause several effects on pregnant mice, such as ovarian failure, interference with hormone secretion by affecting the steroidogenesis-related gene expression, and oxidative stress. The sex ratio of litters was also influenced by prenatal exposure to pure glyphosate.
Show more [+] Less [-]Distribution and predictors of urinary polycyclic aromatic hydrocarbon metabolites in two pregnancy cohort studies
2018
Cathey, Amber | Ferguson, Kelly K. | McElrath, Thomas F. | Cantonwine, David E. | Pace, Gerry | Alshawabkeh, Akram | Cordero, Jose F. | Meeker, John D.
Pregnant women and their fetuses represent susceptible populations to environmental contaminants. Exposure to polycyclic aromatic hydrocarbons (PAHs) among pregnant women may contribute to adverse birth outcomes such as preterm birth. Multiple previous studies have assessed airborne sources of PAHs among pregnant women but few have measured urinary PAH metabolites which can capture total exposure through multiple routes. The aim of this study was to bridge this knowledge gap by assessing longitudinal urinary PAH metabolite concentrations over two time points in pregnancy cohorts in Boston (N = 200) and Puerto Rico (N = 50) to better understand exposure distributions throughout pregnancy and how they relate to demographic factors. Urine samples were analyzed for 1-NAP, 2-NAP, 2-FLU, 1-PHE, 2,3-PHE, 4-PHE, 9-PHE, and 1-PYR. Concentrations of 2-NAP, 1-PYR, and 4-PHE were higher in Puerto Rico, while all other metabolites were present in higher concentrations in Boston. In Puerto Rico, intraclass correlation coefficients (ICC) were weak to moderate, ranging from 0.06 to 0.42. PAH metabolite concentrations were significantly higher among younger, heavier (except 1-NAP and 9-PHE), and less educated individuals in Boston only. Consistent significant associations between PAH concentrations and measured covariates were not found in Puerto Rico. Our results suggest that potentially important differences in PAH exposure exist between these two populations. Additionally, our results indicate that multiple urinary measurements are required to accurately assess PAH exposure throughout pregnancy.
Show more [+] Less [-]Repeated measures of prenatal phthalate exposure and maternal hemoglobin concentration trends: The Ma'anshan birth cohort (MABC) study
2018
Zhu, Yuan-duo | Zhu, Bei-bei | Gao, Hui | Huang, Kun | Xu, Yuan-yuan | Yan, Shuang-qin | Zhou, Shan-shan | Cai, Xiu-xiu | Zhang, Qiu-feng | Qi, Juan | Jin, Zhong-xiu | Sheng, Jie | Pan, Wei-jun | Hao, Jia-hu | Zhu, Peng | Tao, Fang-biao
A prospective cohort study of a Chinese population was conducted to investigate the relationship between prenatal phthalates exposure and maternal hemoglobin or anemia. Based on the Ma'anshan Birth Cohort study, 7 phthalate metabolites were quantified in spot pregnancy urine samples (n = 9263) from 3269 pregnant women during each trimester. The maternal hemoglobin concentrations were obtained from electronic medical records at the same three time points for each participant during pregnancy. Anemia was defined as a hemoglobin concentration below 110 g/L in pregnant women. Repeated measures and trimester-specific analyses were used to estimate the effects of phthalates exposure on maternal hemoglobin and anemia. The prevalence of anemia was 3.6%, 27.0%, and 26.5% during the first, second and third trimester, respectively. Repeated measures analysis showed that hemoglobin concentrations decreased by 0.55, 0.19, 0.57, 0.49, and 0.54 g/L with each 1 ln-transformed concentration increase of MBP, MBzP, MEHP, MEOHP, and MEHHP, respectively. Exposure to MMP, MBP, MEHP, MEOHP, and MEHHP increased the risk of anemia by 1.11-fold, 1.21-fold, 1.20-fold, 1.13-fold, and 1.16-fold, respectively. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. This is the first study focusing on the effect of prenatal phthalate exposures on hemoglobin or anemia in pregnant Chinese women. We found that prenatal phthalates exposure not only decreased the concentrations of hemoglobin but also showed associations with the prevalence of anemia. Associations appeared stronger for the subsample representing women pregnant with a male fetus than those pregnant with a female fetus. Anemia remains a moderate public health problem in China, and effective measures should be implemented.
Show more [+] Less [-]Maternal–fetal transfer rates of PCBs, OCPs, PBDEs, and dioxin-like compounds predicted through quantitative structure–activity relationship modeling
2018
Eguchi, Akifumi | Hanazato, Masamichi | Suzuki, Norimichi | Matsuno, Yoshiharu | Todaka, Emiko | Mori, Chisato
The present study aims to predict the maternal–fetal transfer rates of the polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), and dioxin-like compounds using a quantitative structure–activity relationship model. The relation between the maternal–fetal transfer rate and the contaminants’ physicochemical properties was investigated by multiple linear regression (MLR), partial least square regression (PLS), and random forest regression (RF). The 10-fold cross-validation technique estimated low predictive performances for both MLR and PLS models (R ²CV = 0.425 ± 0.0964 for MLR and R ²CV = 0.492 ± 0.115 for PLS) and is in agreement with an external test (R ²ₚᵣₑd = 0.129 for MLR and R ²ₚᵣₑd = 0.123 for PLS). In contrast, the RF model exhibits good predictive performance, estimated through 10-fold cross-validation (R ²CV = 0.566 ± 0.0885) and an external test set (R ²ₚᵣₑd = 0.519). Molecular weight and polarity were selected in all models as important parameters that may predict the ability of a molecule to cross the placenta to the fetus.
Show more [+] Less [-]Alteration of adaptive behaviors of progeny after maternal mobile phone exposure
2018
Petitdant, Nicolas | Lecomte, Anthony | Robidel, Franck | Gamez, Christelle | Blazy, Kelly | Villégier, Anne-Sophie
Exposure of pregnant women to radiofrequency (RF) devices raises questions on their possible health consequences for their progeny. We examined the hazard threshold of gestational RF on the progeny’s glial homeostasis, sensory-motor gating, emotionality, and novelty seeking and tested whether maternal immune activation would increase RF toxicity. Pregnant dams were daily restrained with loop antennas adjoining the abdomen (fetus body specific absorption rates (SAR): 0, 0.7, or 2.6 W/kg) and received three lipopolysaccharide (LPS) intra-peritoneal injections (0 or 80 μg/kg). Scores in the prepulse startle inhibition, fear conditioning, open field, and elevated plus maze were assessed at adolescence and adulthood. Glial fibrillary acidic protein (GFAP) and interleukines-1β (ILs) were quantified. LPS induced a SAR-dependent reduction of the prepulse startle inhibition in adults. Activity in the open field was reduced at 2.6 W/kg at adolescence. GFAP and ILs, emotional memory, and anxiety-related behaviors were not modified. These data support the hypothesis that maternal immune activation increased the developmental RF exposure-induced long-term neurobiological impairments. These data support the fact that fetuses who receive combined environmental exposures with RF need special attention for protection.
Show more [+] Less [-]Fetal exposure markers of dioxins and dioxin-like PCBs
2018
Lampa, Erik | Eguchi, Akifumi | Todaka, Emiko | Mori, Chisato
Fetal exposure to polychlorinated biphenyls (PCBs), polychlorinated-p-dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) have been associated with a number of adverse health outcomes. Although the placenta acts as a barrier between the mother and the fetus, these contaminants transfer through the placenta exposing the fetus. Several studies have investigated placental transfer, but few have assessed the co-variation among these contaminants. Maternal blood, cord blood, and cord tissue were collected from 41 Japanese mother-infant pairs and analyzed for dioxin-like PCBs and PCDD/Fs. Hierarchical cluster analysis followed by principal component analysis were used to assess the co-variation. Two stable clusters of dioxin-like PCBs were found in maternal and cord blood. One cluster of low/medium chlorinated dioxin-like PCBs was present in all three matrices with 2,3’,4,4’,5-PeCB(#118) and 3,3’,4,4’,5-PeCB(#126) explaining the majority of the clusters’ variances. Medium/high chlorinated dioxin-like PCBs clustered in maternal blood and cord blood but not in cord tissue. 2,3,4,4’,5-PeCB(#114) and 2,3,3’,4,4’,5,5’-HpCB(#189) explained the majority of the clusters’ variances. There was a substantial correlation between the sum of dioxin-like PCBs and total PCDD/F in all three matrices. The sum of the four suggested PCBs plus 3,3’,4,4’-TeCB(#77) correlated well with total PCDD/F in all three matrices. Apart from the dioxin-like PCBs, little co-variation existed among the studied contaminants. The five PCBs can be used as fetal exposure markers for dioxin and dioxin-like PCBs in maternal and cord blood respectively. In cord tissue, more higher chlorinated dioxin-like PCBs need to be measured as well.
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