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Project description:The health impacts of endocrine disrupting chemicals (EDCs) remain debated and their tissue and molecular targets are poorly understood. Here, we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC Bisphenol A (BPA). Prenatal BPA exposure led to scores of transcriptomic and methylomic alterations in the adipose, hypothalamus, and liver tissues in mouse offspring, with cross-tissue perturbations in lipid metabolism as well as tissue-specific alterations in histone subunits, glucose metabolism and extracellular matrix. Network modeling prioritized main molecular targets of BPA, including Pparg, Hnf4a, Esr1, Srebf1, and Fasn. Lastly, integrative analyses identified the association of BPA molecular signatures with cardiometabolic phenotypes in mouse and human. Our multi-tissue, multi-omics investigation provides strong evidence that BPA perturbs diverse molecular networks in central and peripheral tissues, and offers insights into the molecular targets that link BPA to human cardiometabolic disorders.
2018-10-23 | GSE121604 | GEO
Project description:The health impacts of endocrine disrupting chemicals (EDCs) remain debated and their tissue and molecular targets are poorly understood. Here, we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC Bisphenol A (BPA). Prenatal BPA exposure led to scores of transcriptomic and methylomic alterations in the adipose, hypothalamus, and liver tissues in mouse offspring, with cross-tissue perturbations in lipid metabolism as well as tissue-specific alterations in histone subunits, glucose metabolism and extracellular matrix. Network modeling prioritized main molecular targets of BPA, including Pparg, Hnf4a, Esr1, Srebf1, and Fasn. Lastly, integrative analyses identified the association of BPA molecular signatures with cardiometabolic phenotypes in mouse and human. Our multi-tissue, multi-omics investigation provides strong evidence that BPA perturbs diverse molecular networks in central and peripheral tissues, and offers insights into the molecular targets that link BPA to human cardiometabolic disorders.
2018-10-23 | GSE121603 | GEO
Project description:The health impacts of endocrine-disrupting chemicals (EDCs) remain debated, and their tissue and molecular targets are poorly understood. In this study, we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC bisphenol A (BPA). Prenatal BPA exposure at 5 mg/kg/d, a dose below most reported no-observed-adverse-effect levels, led to tens to thousands of transcriptomic and methylomic alterations in the adipose, hypothalamus, and liver tissues in male offspring in mice, with cross-tissue perturbations in lipid metabolism as well as tissue-specific alterations in histone subunits, glucose metabolism, and extracellular matrix. Network modeling prioritized main molecular targets of BPA, including Pparg, Hnf4a, Esr1, Srebf1, and Fasn as well as numerous less studied targets such as Cyp51 and long noncoding RNAs across tissues, Fa2h in hypothalamus, and Nfya in adipose tissue. Lastly, integrative analyses identified the association of BPA molecular signatures with cardiometabolic phenotypes in mouse and human. Our multitissue, multiomics investigation provides strong evidence that BPA perturbs diverse molecular networks in central and peripheral tissues and offers insights into the molecular targets that link BPA to human cardiometabolic disorders.
| S-EPMC6349005 | biostudies-literature
Project description:Prenatal Bisphenol A Exposure in Mice Induces Multi-tissue Multi-omics Disruptions Linking to Cardiometabolic Disorders
| PRJNA497859 | ENA
Project description:Prenatal Bisphenol A Exposure in Mice Induces Multi-tissue Multi-omics Disruptions Linking to Cardiometabolic Disorders (RRBS)
| PRJNA497864 | ENA
Project description:Prenatal Bisphenol A Exposure in Mice Induces Multi-tissue Multi-omics Disruptions Linking to Cardiometabolic Disorders (RNA-Seq)
| PRJNA497865 | ENA
Project description:MicroRNAs (miRNAs) are non-coding RNA molecules that regulate gene expression. Extensive research has explored the role of miRNAs in the risk for type 2 diabetes (T2D) and coronary heart disease (CHD) using single-omics data, but much less by leveraging population-based omics data. Here we aimed to conduct a multi-omics analysis to identify miRNAs associated with cardiometabolic risk factors and diseases. First, we used publicly available summary statistics from large-scale genome-wide association studies to find genetic variants in miRNA-related sequences associated with various cardiometabolic traits, including lipid and obesity-related traits, glycemic indices, blood pressure, and disease prevalence of T2D and CHD. Then, we used DNA methylation and miRNA expression data from participants of the Rotterdam Study to further investigate the link between associated miRNAs and cardiometabolic traits. After correcting for multiple testing, 180 genetic variants annotated to 67 independent miRNAs were associated with the studied traits. Alterations in DNA methylation levels of CpG sites annotated to 38 of these miRNAs were associated with the same trait(s). Moreover, we found that plasma expression levels of 8 of the 67 identified miRNAs were also associated with the same trait. Integrating the results of different omics data showed miR-10b-5p, miR-148a-3p, miR-125b-5p, and miR-100-5p to be strongly linked to lipid traits. Collectively, our multi-omics analysis revealed multiple miRNAs that could be considered as potential biomarkers for early diagnosis and progression of cardiometabolic diseases.
| S-EPMC7056871 | biostudies-literature
Project description:Prenatal cocaine exposure (PCE) affects neurobehavioral development, however, disentangling direct drug-related mechanisms from contextual effects (e.g., socioeconomic status) has proven challenging in humans. The effects of environmental confounds are minimal immediately after birth thus we aimed to delineate neurobehavioral correlates of PCE in a large cohort of neonates (2-6weeks of age, N=152) with and without drug exposure using resting state functional magnetic resonance imaging (rsfMRI) and developmental assessments at 3months with the Bayley Scales of Infant & Toddler Development, 3rd edition. The cohort included healthy controls and neonates with similar poly-drug exposure±cocaine. We focused on the thalamus given its critical importance in early brain development and its unique positioning in the dopamine system. Our results revealed PCE-related hyper-connectivity between the thalamus and frontal regions and a drug-common hypo-connective signature between the thalamus and motor-related regions. PCE-specific neonatal thalamo-frontal connectivity was inversely related to cognitive and fine motor scores and thalamo-motor connectivity showed a positive relationship with composite (gross plus fine) motor scores. Finally, cocaine by selective-serotonin-reuptake-inhibitor (SSRI) interactions were detected, suggesting the combined use of these drugs during pregnancy could have additional consequences on fetal development. Overall, our findings provide the first delineation of PCE-related disruptions of thalamocortical functional connectivity, neurobehavioral correlations, and drug-drug interactions during infancy.
| S-EPMC4935611 | biostudies-literature
Project description:Experimental laboratory evidence suggests that bisphenol A (BPA), an endocrine disruptor, is a neurodevelopmental toxicant. However, there have been limited and inconclusive results with respect to sex-specific BPA effects on child behavior.We examined the association between prenatal BPA exposure and child behavior, adjusting for postnatal BPA exposure and hypothesizing sex-specific effects.We followed African-American and Dominican women and their children from pregnancy to child's age 5 years, collecting spot urine samples from the mothers during pregnancy (34 weeks on average) and from children between 3 and 4 years of age to estimate BPA exposure. We assessed child behavior between 3 and 5 years of age using the Child Behavior Checklist (CBCL) and used generalized linear models to test the association between BPA exposure and child behavior, adjusting for potential confounders.The analysis was conducted on 198 children (87 boys and 111 girls). Among boys, high prenatal BPA exposure (highest quartile vs. the lowest three quartiles) was associated with significantly higher CBCL scores (more problems) on Emotionally Reactive [1.62 times greater; 95% confidence interval (CI): 1.13, 2.32] and Aggressive Behavior syndromes (1.29 times greater; 95% CI: 1.09, 1.53). Among girls, higher exposure was associated with lower scores on all syndromes, reaching statistical significance for Anxious/Depressed (0.75 times as high; 95% CI: 0.57, 0.99) and Aggressive Behavior (0.82 times as high; 95% CI: 0.70, 0.97).These results suggest that prenatal exposure to BPA may affect child behavior, and differently among boys and girls.
| S-EPMC3440080 | biostudies-other
Project description:Background: How prenatal smoke exposure affects DNA methylation leading to atopic disorders remains to be addressed. Epigenetic biomarkers informative of prenatal smoke exposure and atopic disorders are wanting. Since most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure e induces DNA methylation and searched for predictive epigenetic biomarkers for smoke related atopic disorders. Methods: Methylation differences associated with smoke exposure were screened by Illumina methylation panel for children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors were collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen and their functions were investigated. Results: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p=0.029). TSLP gene was further investigated in a larger sample of 92 children from the cohort. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.59, 95%CI=1.49-8.64; cotinine level 0.10 ng/ml, sensitivity= 77%; specificity = 61%) and with AD (OR=4.77, 95%CI=1.47-15.53). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (per unit: β=－6.69 ng/ml; 95% CIs, －12.80~－0.59; p=0.032). Conclusions: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. Cord blood methylated TSLP 5′CGI may be a potential epigenetic biomarker for environmentally-related atopic disorders. The buffy coat and plasma samples were separated and stored at −80°C. DNA (100 ng-500 ng) was extracted from cord white blood cells. Microarrays have been performed to investigate fourteen samples, which were classified as two groups according to cotinine exposure dosage (7 versus 7 : high exposure verses low exposure).
2013-12-31 | E-GEOD-35222 | biostudies-arrayexpress