Dataset Information

Persistent organic pollutants in Norwegian men from 1979 to 2007: intraindividual changes, age-period-cohort effects, and model predictions.

ABSTRACT: BACKGROUND: Longitudinal monitoring studies of persistent organic pollutants (POPs) in human populations are important to better understand changes with time and age, and for future predictions. OBJECTIVES: We sought to describe serum POP time trends on an individual level, investigate age-period-cohort effects, and compare predicted polychlorinated biphenyl (PCB) concentrations to measured values. METHODS: Serum was sampled in 1979, 1986, 1994, 2001, and 2007 from a cohort of 53 men in Northern Norway and analyzed for 41 POPs. Time period, age, and birth cohort effects were assessed by graphical analyses and mixed-effect models. We derived the predicted concentrations of four PCBs for each sampling year using the CoZMoMAN model. RESULTS: The median decreases in summed serum POP concentrations (lipid-adjusted) in 1986, 1994, 2001, and 2007 relative to 1979 were -22%, -52%, -54%, and -68%, respectively. We observed substantial declines in all POP groups with the exception of chlordanes. Time period (reflected by sampling year) was the strongest descriptor of changes in PCB-153 concentrations. Predicted PCB-153 concentrations were consistent with measured concentrations in the study population. CONCLUSIONS: Our results suggest substantial intraindividual declines in serum concentrations of legacy POPs from 1979 to 2007 in men from Northern Norway. These changes are consistent with reduced environmental exposure during these 30 years and highlight the relation between historic emissions and POP concentrations measured in humans. Observed data and interpretations are supported by estimates from the CoZMoMAN emission-based model. A longitudinal decrease in concentrations with age was evident for all birth cohorts. Overall, our findings support the relevance of age-period-cohort effects to human biomonitoring of environmental contaminants.

SUBMITTER: Nost TH

PROVIDER: S-EPMC3855502 | biostudies-literature | 2013 Nov-Dec

REPOSITORIES: biostudies-literature

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Persistent organic pollutants in Norwegian men from 1979 to 2007: intraindividual changes, age-period-cohort effects, and model predictions.

Nøst Therese Haugdahl TH Breivik Knut K Fuskevåg Ole-Martin OM Nieboer Evert E Odland Jon Øyvind JØ Sandanger Torkjel Manning TM

Environmental health perspectives 20130905 11-12

<h4>Background</h4>Longitudinal monitoring studies of persistent organic pollutants (POPs) in human populations are important to better understand changes with time and age, and for future predictions.<h4>Objectives</h4>We sought to describe serum POP time trends on an individual level, investigate age-period-cohort effects, and compare predicted polychlorinated biphenyl (PCB) concentrations to measured values.<h4>Methods</h4>Serum was sampled in 1979, 1986, 1994, 2001, and 2007 from a cohort of ...[more]

PMID: 24007675

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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

Persistent organic pollutants in Norwegian men from 1979 to 2007: intraindividual changes, age-period-cohort effects, and model predictions.

Publications

Persistent organic pollutants in Norwegian men from 1979 to 2007: intraindividual changes, age-period-cohort effects, and model predictions.

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