Dataset Information

Selected persistent organic pollutants in human placental tissue from the United States.

ABSTRACT: Emerging and legacy environmental pollutants such as polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and organochlorine pesticide metabolite DDE are found in human placenta, indicating prenatal exposure, but data from the United States are sparse. We sought to determine concentrations of these compounds in human placentae as part of a formative research project conducted by the National Children's Study Placenta Consortium. A total of 169 tissue specimens were collected at different time points post delivery from 43 human placentae at three U.S. locations, and analyzed by gas chromatography coupled with mass spectrometry following extraction using matrix solid phase dispersion. PBDEs, PCBs, and DDE were detected in all specimens. The concentrations of 10 PBDEs (?10PBDEs), 32 PCBs (?32PCBs) and p,p'-DDE were 43-1723, 76-856 and 10-1968pgg(-1) wet weight, respectively, in specimens collected shortly after delivery. Significant geographic differences in PBDEs were observed, with higher concentrations in placentae collected in Davis, CA than in those from Rochester, NY or Milwaukee, WI. We combined these with other published data and noted first-order declining trends for placental PCB and DDE concentrations over the past decades, with half-lives of about 5 and 8years, respectively. The effect of time to tissue collection from refrigerated placentae on measured concentrations of these three classes of persistent organic pollutants was additionally examined, with no significant effect observed up to 120h. The results of this work indicate that widespread prenatal exposure to persistent organic pollutants in the United States continues.

SUBMITTER: National Children’s Study Placenta Consortium

PROVIDER: S-EPMC3966927 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Selected persistent organic pollutants in human placental tissue from the United States.

Nanes Jessica A JA Xia Yulin Y Dassanayake R M A Priyanthi S RMAPS Jones Rachael M RM Jones Rachael M RM Li An A Stodgell Christopher J CJ Walker Cheryl C Szabo Sara S Leuthner Steve S Durkin Maureen S MS Moye Jack J Miller Richard K RK

Chemosphere 20140131

Emerging and legacy environmental pollutants such as polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and organochlorine pesticide metabolite DDE are found in human placenta, indicating prenatal exposure, but data from the United States are sparse. We sought to determine concentrations of these compounds in human placentae as part of a formative research project conducted by the National Children's Study Placenta Consortium. A total of 169 tissue specimens were collected ...[more]

PMID: 24485817

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Project description:Human exposure to environmental chemicals as persistent organic pollutants (POPs) is usually assessed considering each pollutant individually, with little attention to concentrations of mixtures in individuals or social groups. Yet, it may be relatively common for humans to have low and high concentrations of numerous POPs. The study objectives were to analyze the number of POPs detected per person at high concentrations in the U.S. population, and the associations between such type of indicators and socioeconomic factors as gender, race / ethnicity, education, and poverty level. From 91 POPs analyzed in serum samples of 4,739 individuals in three subsamples of the National Health and Nutrition Examination Survey (NHANES) 2003-2004 (the last period with valid updated individual data for the compounds considered in the present study), we computed the number of POPs whose serum concentrations were above selected cutoff points. POPs included were 13 organochlorine compounds (OCs), 10 polybrominated diphenyl ethers (PBDEs), the polybrominated biphenyl (PBB) 153, 38 polychlorinated biphenyls (PCBs), 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/Fs), and 12 perfluorinated compounds (PFCs). Over 13% of participants had ≥10 of the 37 most detected POPs each at a concentration in the top decile (P90). Over 30% of subjects with total toxic equivalency (TEQ) ≥P75, had ≥10 of 24 POPs not included in TEQ calculations at concentrations ≥P90. Compared to non-Hispanic whites, the adjusted odds ratio of having ≥10 of the 37 POPs at P90 was 9.2 for non-Hispanic blacks and 0.18 for Mexican Americans. Poverty, body mass index, age, and gender were also independently associated with having ≥10 POPs in the top decile. More than one tenth of the US population may have ≥10 POPs each at concentrations in the top decile. Such pattern is nine times more frequent in Non-Hispanic blacks and four times less frequent in Mexican Americans than in non-Hispanic whites.

Project description:BACKGROUND:Prenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies. RESULTS:Our analysis focused on POPs with more than 80% plasma concentrations above the limit of quantification, including 3 organochlorine pesticides (hexachlorobenzene, trans-nonachlor, p,p'-dichlorodiphenyldichloroethylene), 1 polybrominated diphenyl ether (PBDE 47), 3 polychlorinated biphenyls (138/158, 153, 180), and 6 poly- and perfluorinated alkyl substances (PFASs) (perfluorodecanoic acid, perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluoroundecanoic acid (PFUnDA)). Using 5% false discovery rate, POPs were associated with a total of 214 differentially methylated CpG sites (nominal p values ranging from 2.61 × 10-21 to 2.11 × 10-7). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3, and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 (TUSC3) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated (p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated (p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs). CONCLUSIONS:DNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures.

Project description:Exposure to persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), has historically been linked to population collapses in wildlife. Despite international regulations, these legacy chemicals are still currently detected in women of reproductive age, and their levels correlate with reduced ovarian reserve, longer time-to-pregnancy, and higher risk of infertility. However, the specific modes of action underlying these associations remain unclear. Here, we examined the effects of five commonly occurring POPs − hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethylene (DDE), 2,3,3′,4,4′,5-hexachlorobiphenyl (PCB156), 2,2′,3,4,4′,5,5′-heptachlorobiphenyl (PCB180), perfluorooctane sulfonate (PFOS) − and their mixture on human ovaries in vitro. We exposed human ovarian cancer cell lines COV434, KGN, and PA1 as well as primary ovarian cells for 24 h, and ovarian tissue containing unilaminar follicles for 6 days. RNA-sequencing of samples exposed to concentrations covering epidemiologically relevant levels revealed significant gene expression changes related to central energy metabolism in the exposed cells, indicating glycolysis, oxidative phosphorylation, fatty acid metabolism, and reactive oxygen species as potential shared targets of POP exposures in ovarian cells. Alpha-enolase (ENO1), lactate dehydrogenase A (LDHA), cytochrome C oxidase subunit 4I1 (COX4I1), ATP synthase F1 subunit alpha (ATP5A), and glutathione peroxidase 4 (GPX4) were validated as targets through qPCR in additional cell culture experiments in KGN. In ovarian tissue cultures, we observed significant effects of exposure on follicle growth and atresia as well as protein expression. All POP exposures, except PCB180, decreased unilaminar follicle proportion and increased follicle atresia. Immunostaining confirmed altered expression of LDHA, ATP5A, and GPX4 in the exposed tissues. Moreover, POP exposures modified ATP production in KGN and tissue culture. In conclusion, our results demonstrate the disruption of cellular energy metabolism as a novel mode of action underlying POP-mediated interference of follicle growth in human ovaries.

Dataset Information

Selected persistent organic pollutants in human placental tissue from the United States.

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Selected persistent organic pollutants in human placental tissue from the United States.

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