Genome‑wide analysis of sex‑specifc diferences in the mother–child PELAGIE cohort exposed to organophosphate metabolites
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE209943 | GEO | 2022/11/10
REPOSITORIES: GEO
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Project description:Genome‑wide analysis of sex‑specifc diferences in the mother–child PELAGIE cohort exposed to organophosphate metabolites
| PRJNA863109 | ENA
Project description:In recent decades, the detrimental effects of environmental contaminants on human health have become a serious public concern. Organophosphate (OP) pesticides are widely used in agriculture, and the negative impacts of OP and its metabolites on human health have been demonstrated. We hypothesized that exposure to OPs during pregnancy could impose damaging effects on the fetus by affecting various processes. We analyzed sex-specific epigenetic responses in the placenta samples obtained from the mother-child PELAGIE cohort. We assayed the telomere length and mitochondrial copy numbers using genomic DNA. We analyzed H3K4me3 by using chromatin immunoprecipitation followed by qPCR (ChIP‒qPCR) and high-throughput sequencing (ChIP-seq). The human study was confirmed with mouse placenta tissue analysis. Our study revealed a higher susceptibility of male placentas to OP exposure. Specifically, we observed telomere length shortening and an increase in γH2AX levels, a DNA damage marker. We detected lower histone H3K9me3 occupancy at telomeres in diethylphosphate (DE)-exposed male placentas than in nonexposed placentas. We found an increase in H3K4me3 occupancy at the promoters of thyroid hormone receptor alpha (THRA), 8-oxoguanine DNA glycosylase (OGG1) and insulin-like growth factor (IGF2) in DE-exposed female placentas. H3K4me3 occupancy at PPARG was increased in both male and female placentas exposed to dimethylphosphate (DM). The genome-wide sequencing of selected samples revealed sex-specific differences induced by DE exposure. Specifically, we found alterations in H3K4me3 in genes related to the immune system in female placenta samples. In DE-exposed male placentas, a decrease in H3K4me3 occupancy at development-related, collagen and angiogenesis-related genes was observed. Finally, we observed a high number of NANOG and PRDM6 binding sites in regions with altered histone occupancy, suggesting that the effects were possibly mediated via these factors. Our data suggest that in utero exposure to organophosphate metabolites affects normal placental development and could potentially impact late childhood.
| S-EPMC10192208 | biostudies-literature
Project description:Prenatal maternal stress has a negative impact on child health but the mechanisms through which maternal stress affects child health are unclear. Epigenetic variation, such as DNA methylation, is a likely mechanistic candidate as DNA methylation is sensitive to environmental insults and can regulate long-term changes in gene expression. We recruited mother-newborn dyads in the Democratic Republic of Congo to investigate the effects of maternal stress on DNA methylation in mothers and newborns. We used four measures of maternal stress to capture a range of stressful experiences: general trauma, sexual trauma, war trauma, and chronic stress. We identified differentially methylated positions (DMPs) associated with general trauma, sexual trauma, and war trauma in both mothers and newborns. No DMPs were associated with chronic stress. Sexual trauma was positively associated with epigenetic age acceleration across several epigenetic clocks in mothers. General trauma and war trauma were positively associated with newborn epigenetic age acceleration using the extrinsic epigenetic age clock. We tested the top DMPs for enrichment of DNase I hypersensitive sites (DHS) and found no enrichment in mothers. In newborns, top DMPs associated with war trauma were enriched for DHS in embryonic and fetal cell types. Finally, one of the top DMPs associated with war trauma in newborns also predicted birthweight, completing the cycle from maternal stress to DNA methylation to newborn health outcome. Our results indicate that maternal stress is associated with site-specific changes in DNAm and epigenetic age acceleration in both mothers and newborns.
2023-06-08 | GSE224363 | GEO
Project description:Prenatal maternal stress has a negative impact on child health but the mechanisms through which maternal stress affects child health are unclear. Epigenetic variation, such as DNA methylation, is a likely mechanistic candidate as DNA methylation is sensitive to environmental insults and can regulate long-term changes in gene expression. We recruited mother-newborn dyads in the Democratic Republic of Congo to investigate the effects of maternal stress on DNA methylation in mothers and newborns. We used four measures of maternal stress to capture a range of stressful experiences: general trauma, sexual trauma, war trauma, and chronic stress. We identified differentially methylated positions (DMPs) associated with general trauma, sexual trauma, and war trauma in both mothers and newborns. No DMPs were associated with chronic stress. Sexual trauma was positively associated with epigenetic age acceleration across several epigenetic clocks in mothers. General trauma and war trauma were positively associated with newborn epigenetic age acceleration using the extrinsic epigenetic age clock. We tested the top DMPs for enrichment of DNase I hypersensitive sites (DHS) and found no enrichment in mothers. In newborns, top DMPs associated with war trauma were enriched for DHS in embryonic and fetal cell types. Finally, one of the top DMPs associated with war trauma in newborns also predicted birthweight, completing the cycle from maternal stress to DNA methylation to newborn health outcome. Our results indicate that maternal stress is associated with site-specific changes in DNAm and epigenetic age acceleration in both mothers and newborns.
2023-06-08 | GSE224364 | GEO
Project description:BackgroundHumans are ubiquitously exposed to flame retardants, including organophosphate esters (OPEs), through direct contact with consumer products or exposure through household dust. Children are at increased risk because of their proximity to dust, hand-to-mouth activity, and the importance of childhood as a critical period in neurodevelopment.ObjectivesTo quantify differences in exposure levels between mothers and children (three to six years of age), we analyzed urinary metabolites of OPEs. We additionally assessed the ability of silicone wristbands (measuring ambient exposure) to predict urinary metabolite concentrations.MethodsWe selected 32 mother and child dyads from an existing cohort. Participants provided baseline urine samples and wore wristbands for one week. After the first week, they returned their wristbands and provided a second urine sample. During the second week, participants wore a second wristband that they returned at the end of week two with a third and final urine sample.ResultsWe found significantly higher levels of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) (p < 0.001) and lower levels of bis(1-chloro-2-isopropyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) (p < 0.001) in children's urine samples compared to mothers' samples at baseline. We found that triphenylphosphate (TPHP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP), and tris(1-chloro-2-propyl) phosphate (TCIPP) measured in wristbands predicted their respective metabolite levels in urine.ConclusionChildren had higher levels than mothers for two of six flame retardant metabolites measured in urine. Generally, wristband measurements positively predicted internal dose. As little is known about the health effects of OPEs on child development, future research is needed to determine the impact of differential exposure.
| S-EPMC6460923 | biostudies-literature
Project description:This study contrasts the expression profiles of peripheral blood leukocytes from third trimester pregnant mothers, with cord blood leukocytes from their newborn children. It is a companion to (GSE21311). After normalization for RNA integrity, major principal components of the variation were found to distinguish individuals. Transmission of gene expression profiles from mother to child was documented, along with differences between gestational diabetic, obese, and normal weight mothers and their children.
2011-01-01 | GSE21342 | GEO
Project description:CD8+ T-cells provide robust anti-viral immunity, yet how epitope-specific T-cells evolve across the human lifespan is unknown. We defined CD8+ T-cell immunity directed at the prominent influenza epitope, HLA-A*02:01-M158-66 (A2/M158) across four age groups (newborns, children, adults and elderly) ex vivo at phenotypic, single cell sequence (transcriptomic), clonal and functional levels. We identified a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resembled those observed in newborns and children, despite being clonally-different. However, only child- and adult-derived A2/M158+CD8+ T-cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T-cells, which was linked to highly functional public TCRab-signatures. Suboptimal TCRab-signatures detected in older adults led to poorer proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. Our study suggests that priming T-cells at different stages of life might greatly affect CD8+ T-cell responses towards viral infections.
2023-08-16 | GSE237817 | GEO
Project description:This study contrasts the expression profiles of peripheral blood leukocytes from third trimester pregnant mothers, with cord blood leukocytes from their newborn children. It is a companion to (GSE21311). After normalization for RNA integrity, major principal components of the variation were found to distinguish individuals. Transmission of gene expression profiles from mother to child was documented, along with differences between gestational diabetic, obese, and normal weight mothers and their children. 56 individulas (Brisbane, Australia) were sampled for the mother-newborn study, under informed consent. 19 mothers sample were collected in the last month of pregnancy (between 30th and 36th week of pregnancy) and 37 cord blood samples were obtained at birth from newborn babies. Mothers having BMI values over 30 before pregnancy were classified as obese. From the 37 newborn babies, 10 were born to obese mothers, 8 to gestational diabetic mothers (with a wide range of body mass indices), and 19 to normal-weight mothers. There were 16 mother-newborn pairs in the dataset. RNA from each was hybridized to an Illumina HT12 array.
2011-01-01 | E-GEOD-21342 | biostudies-arrayexpress
Project description:Several studies suggest that exposure to organophosphate insecticides (OP) during pregnancy impairs neurodevelopment in children.We evaluated associations between biomarkers of prenatal and postnatal OP exposure and cognitive function of 6-year-olds in a French longitudinal birth cohort.In 2002-2006, the PELAGIE mother-child cohort enrolled pregnant women from Brittany. For a random subcohort, we measured nonspecific dialkylphosphate metabolites (DAP) of OP in one maternal urine sample, collected before 19 weeks' gestation, and in one urine sample collected from their 6-year-old children. Six subtests of the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) were administered when the children were 6 years of age to evaluate cognitive function (n = 231). Linear regression models controlling for factors including maternal intelligence and the Home Observation for Measurement of the Environment score were used.WISC-IV scores were not significantly associated with prenatal or childhood total DAP metabolites. WISC verbal comprehension score was significantly higher in association with the highest maternal urinary concentrations of diethylphosphate (DE) metabolites (5.5; 95% CI: 0.8, 10.3 for > 13.2 nmol/L vs. < LOQ), whereas WISC working memory score was significantly lower in association with the highest urinary concentrations of DE metabolites at age 6 years (-3.6; 95% CI: -7.8, -0.6 for > 11.1 nmol/L vs. < LOD).We found no evidence that prenatal OP exposure adversely affected cognitive function in 6-year-olds, perhaps because of the population's socioeconomic status, which was higher than in previous studies, though other causal and noncausal explanations are also possible. The negative association between WISC score and concurrent DE urinary concentrations requires replication by longitudinal studies investigating childhood OP exposure.Cartier C, Warembourg C, Le Maner-Idrissi G, Lacroix A, Rouget F, Monfort C, Limon G, Durand G, Saint-Amour D, Cordier S, Chevrier C. 2016. Organophosphate insecticide metabolites in prenatal and childhood urine samples and intelligence scores at 6 years of age: results from the mother-child PELAGIE cohort (France). Environ Health Perspect 124:674-680; http://dx.doi.org/10.1289/ehp.1409472.
| S-EPMC4858392 | biostudies-literature