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The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms.

ABSTRACT: Persistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to uncover the effects of POPs on the endocrine and nervous systems and on cancer, few focus on the relationship between low-dose POPs and public health. Here, we attempt to determine the relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation.We recruited 121 subjects who visited Kyungpook National University Medical Center for health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls (PCBs) and 23 types of organochlorine pesticides (OCP). Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms.Based on our results, abdominal discomfort showed an inverse relationship with several PCBs and an inverted U-shaped relationship with several other OCPs including pp-DDD and pp-DDT. The effects of pp-DDD and pp-DDT on abdominal discomfort were similar to those of OCPs on obesity and metabolic syndrome.Our results suggest that mild and unspecified gastrointestinal symptoms with no clear causes could be related to POP levels.

SUBMITTER: Kim HM

PROVIDER: S-EPMC5541173 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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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.

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The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms.

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