Effects of Polybrominated Diphenyl Ether (PBDE) Mixture on estrogen receptor positive (ER+) patient-derived tumor xenograft (PDX) model
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE119587 | GEO | 2019/03/04
REPOSITORIES: GEO
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Project description:Effects of Polybrominated Diphenyl Ether (PBDE) Mixture on estrogen receptor positive (ER+) patient-derived tumor xenograft (PDX) model
| PRJNA489668 | ENA
Project description:Brominated flame retardants (BFRs) are incorporated into consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female fertility. Our goal was to elucidate effects of a mixture reflecting human follicular fluid levels of polybrominated flame retardants (PBDEs), the major class of BFRs, on an immortalized human granulosa cell line, the KGN cell line. We showed that cell viability was altered and oxidative stress was induced, as reflected by increased reactive oxygen species formation, at 20 µM of the PBDE mixture. Transcriptomic analysis revealed that several genes showing an altered expression after the PBDE treatment were involved in oxidative stress signaling pathways. Significant dose-dependent reduction of progesterone and estradiol levels was measured after PBDE treatment; expression of genes involved in steroid hormone metabolism, namely CYP1A1, was significantly affected by PBDEs. Treatment with the PBDE mixture also modified genes encoding for members of the transforming growth factor β superfamily like inhibins and cytokines, including the pro-inflammatory factor, interleukin-6 (IL6). Concentration of IL-6 in KGN cell culture media was consistently increased after treatment with the PBDE mixture. Our results clearly demonstrate that the PBDEs detected in human follicular fluid alter human granulosa cell functions by inducing oxidative stress, disrupting steroidogenesis and triggering an inflammatory response. This strengthens the fact that PBDEs are detrimental to ovarian functions and thus, to women’s reproductive health.
2016-05-25 | GSE77963 | GEO
Project description:Polybrominated diphenyl ethers (PBDEs) are flame retardant chemicals used in consumer products. They are common contaminants in human serum and associated with adverse health effects. Our objectives were to characterize PBDE serum concentrations in a New England cohort and assess temporal variability of this exposure biomarker over a one-year period. We collected three repeated measurements at six-month intervals from 52 office workers from the greater Boston (MA, United States) area from 2010 to 2011. The intraclass correlation coefficient for BDEs 28, 47, 99, 100, and 153 ranged from 0.87 to 0.99, indicating that a single serum measurement can reliably estimate exposure over a one-year period. This was true for both lipid adjusted and nonlipid adjusted concentrations. The kappa statistics, quantifying the level of agreement of categorical exposure classification, based on medians, tertiles, or quartiles ranged from 0.67 to 0.90. Some congeners showed nonsignificant increases from sampling round 1 (winter) to round 2 (summer) and significant decreases from round 2 to round 3 (winter). This study highlights the high reliability of a single serum PBDE measurement for use in human epidemiologic studies.
| S-EPMC4270390 | biostudies-literature
Project description:Extensive use of polybrominated diphenyl ethers (PBDEs) has resulted in widespread environmental distribution and concerns remain about risks to human health and ecosystems from legacy PBDE contamination. Though bioremediation has been proven to be a cost-effective and efficient technology for treating halogenated pollutants in situ, application of bioremediation technologies at PBDE-contaminated sites is restricted by a lack of knowledge about functional PBDE-dehalogenating microbes. In the current study, we observed distinct PBDE-dehalogenation activity by three previously isolated Dehalococcoides mccartyi strains (CG1, CG4, and 11a5). PBDE debromination proceeded via distinct pathways in each D. mccartyi strain and involved previously characterized (TceA11a5, PcbA1, and PcbA4) and uncharacterized (11a5_e001) reductive dehalogenases (RDase), suggesting that this phenotype may be more widespread among the Dehalococcoides than is currently recognized.
2022-05-26 | PXD026932 | Pride
Project description:BACKGROUND:Prenatal polybrominated diphenyl ether (PBDE) exposure has been associated with decrements in IQ and increased attention deficit/hyperactivity disorder related behaviors in children; however, data are limited for the role of postnatal exposures. OBJECTIVES:We investigated the association between a series of childhood PBDE concentrations and Full-Scale Intelligence Quotient (FSIQ) and externalizing problems at 8 years. METHODS:We used data from 208 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort. Child serum PBDEs were measured at 1, 2, 3, 5, and 8 years; missing serum PBDE concentrations were estimated via multiple imputation. The Wechsler Intelligence Scales for Children-IV and the Behavior Assessment System for Children-2 was used to assess intelligence and externalizing behavior, respectively, in children at 8 years. We used multiple informant models to estimate associations between repeated lipid-adjusted PBDEs and child neurobehavior and to test for windows of susceptibility. RESULTS:Postnatal exposure to PBDE congeners (- 28, - 47, - 99, - 100, and - 153) at multiple ages was inversely associated with FSIQ at 8 years. For instance, a 10-fold increase in BDE-153 concentrations at 2, 3, 5, and 8 years were all related to lower FSIQ at age 8 (? for 3 years: - 7.7-points, 95% CI - 12.5, - 2.9; ? for 8 years: - 5.6-points, 95% CI - 10.8, - 0.4). Multiple PBDE congeners at 8 years were associated with increased hyperactivity and aggressive behaviors at 8 years. CONCLUSIONS:Postnatal PBDE exposure was associated with decrements in FSIQ and increases in hyperactivity and aggressive behaviors.
| S-EPMC5567986 | biostudies-literature
Project description:BACKGROUND:Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood. METHODS:We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 ± 3 weeks gestation and in child serum at 1-3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years. RESULTS:Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ∑PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI -40.8%, -11.3%) in TSH. A ten-fold increase in prenatal ∑PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT3). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T4 (FT4) in males. Prenatal ∑PBDEs were not associated with TT4, FT4, or total T3. CONCLUSIONS:These findings suggest an inverse relationship between prenatal ∑PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males.
| S-EPMC5997562 | biostudies-literature
Project description:Serum concentrations of PBDEs were measured using gas chromatography-tandem mass spectrometry in 80 children aged 15-71 months. Demographic and behavioral data were collected on parental questionnaires; a research nurse recorded anthropometric measures and insurance status. For a subset of children (n = 17), PBDEs were measured in house dust and child handwipes sampled during a home visit. In linear and Tobit regression, log-transformed PBDE congeners were modeled as a function of child characteristics, including neighborhood-level socioeconomic indicators. BDE congeners 47, 99, and 100 were highly correlated and summed for analysis; BDE-153 was examined individually. PBDE serum concentrations were associated with socioeconomic factors; for example, a $20,000 increase in median household income in a child's ZIP code was associated with a 34% decrease (95%CI = 14-49%) in BDE-153 and a 26% decrease (95%CI = 6-42%) in ?BDE-47,-99,-100. Lower body-mass index (BMI) z-score and household smoking were strong predictors of higher BDE-153 levels. Among children who participated in a home visit, serum PBDE was positively correlated with handwipe PBDE (Spearman r ?BDE-47, -99, -100 = 0.48, p = 0.09), but not dust PBDE. Results indicate socioeconomic factors and BMI are strong predictors of serum PBDE levels among young children. PBDEs measured on handwipes are more predictive of serum PBDE levels than vacuum-collected dust.
| S-EPMC5538570 | biostudies-literature
Project description:A recent systematic review (SR) and meta-analysis of human studies found an association between prenatal serum polybrominated diphenyl ethers (PBDE) concentrations and a decrease in the IQ of children. A SR of experimental developmental animal PBDE-mediated neurotoxicity studies was performed in the present study. Outcomes assessed included measures related to learning, memory, and attention, which parallel the intelligence-related outcomes evaluated in the human studies SR. PubMed, Embase, and Toxline were searched for relevant experimental non-human mammalian studies. Evaluation of risk of bias (RoB) and overall body of evidence followed guidance developed by the National Toxicology Program. Animal studies using varying designs and outcomes were available for BDEs 47, 99, 153, 203, 206, and 209 and the technical mixture DE-71. Study reporting of methods and results was often incomplete leading to concerns regarding RoB. A meta-analysis of 6 Morris water maze studies showed evidence of a significant increase in last trial latency (effect size of 25.8 [CI, 20.3 to 31.2]) in PBDE-exposed animals with low heterogeneity. For most endpoints, there were unexplained inconsistencies across studies and no consistent evidence of a dose-response relationship. There is a "moderate" level of evidence that exposure to BDEs 47, 99, and 209 affects learning. For other PBDEs and other endpoints, the level of evidence was "low" or "very low". The meta-analysis led to stronger conclusions than that based upon a qualitative review of the evidence. The SR also identified RoB concerns that might be remedied by better study reporting.
| S-EPMC6786272 | biostudies-literature
Project description:We measured levels of 10 polybrominated diphenyl ether (PBDE) congeners in serum collected during pregnancy and at delivery from 416 pregnant, predominantly immigrant, women living in Monterey County, CA. The most frequently detected congeners were BDE-47, -99, -100, and -153, all components of the penta mixture, detected in >97% of samples. We used multivariable regression models to examine factors associated with exposure to individual PBDE congeners as well as their total summed concentration (ng/g lipid). Prenatal and delivery total PBDE levels were correlated between sampling times (n = 21; Pearson r = 0.99, p < 0.001). In multivariable models, total PBDE levels increased significantly with time residing in the U.S. (p < 0.001) and among women with ?3 pieces of stuffed furniture in their homes (p < 0.05). Women's total PBDE levels increased 4.0% (95% CI = 2.8, 5.3) for each additional year residing in the U.S., after adjustment for prepregnancy BMI, weight gain during pregnancy, and SES. Having ?3 pieces of stuffed furniture in the home was associated with a 26.8% (95% CI = 2.0, 57.5) increase in women's serum PBDE levels. Findings suggest PBDE indoor contamination in California homes is contributing to human exposures in a population of recent immigrants.
| S-EPMC3285470 | biostudies-literature
Project description:Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (?=4.6, 95% CI 0.5, 8.7) and BDE-153 (?=4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.
| S-EPMC5726937 | biostudies-literature