Exposure to several persistent organic pollutants (POPs) in pregnant women and newborn infants and associated endocrine disruption effects
산모-태아의 잔류성 유기오염물질 노출과 내분비계 교란 영향

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보건대학원 보건학과
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서울대학교 대학원
Polychlorinated biphenyls (PCBs)Polybrominated diphenyl ethers (PBDEs)Organochlorine pesticides (OCPs)pregnant womenfetusthyroid hormoneadiponectinleptinbreast milkCHECK Panel
학위논문 (박사)-- 서울대학교 보건대학원 : 보건학과, 2015. 2. 최경호.
Many of the persistent organic pollutants (POPs) had been banned several decades ago. However, most of these compounds, including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) have been frequently detected in various environmental media, biota, and human biological samples worldwide. In addition, new POPs - such as polybrominated diphenyl ethers (PBDEs) - have also been frequently detected because of their extensive use and bioaccumulative characteristics. Among various toxic effects of POPs, endocrine disruption that may link to changes in growth and development, metabolic disorders and obesity is one of the important adverse health effects.
Thyroid hormones and adipokines are key hormones related to normal development and energy metabolism. Early life stages are particularly susceptible to these hormones and the endocrine disruption. Endocrine disrupting effect during these sensitive periods may lead to permanent adverse effects in later stages of life. Therefore, association between POPs exposure and endocrine disruption among the susceptible human populations, including fetuses, newborn infants, and pregnant women deserves scrupulous investigation. However, current understanding on endocrine disruption effects of POPs is still limited among these vulnerable populations and previously reported results are frequently controversial. In order to address these issues, the present study investigates the association between POPs exposure and thyroid hormones or adipokine levels among pregnant women or matching newborns.
For this purpose, pregnant women and their matching newborn infants without any known occupational exposure pathways to major POPs were recruited from five university hospitals located in four cites of South Korea in 2011-2012 (Childrens Health and Environmental Chemicals of Korea Panel: CHECK Panel). Maternal and cord blood serum samples were collected at delivery, and breast milk samples were collected between 15th and 30th day of lactation. Target chemicals including 19 OCPs, 19 PCBs, and 19 PBDEs, and hormones were measured in serum samples, and chemicals which were detected > 60% and sum of the isomers (ΣPCB, ΣPBDE, Σdichlorodiphenyltrichloroethane (DDT), Σchlordane (CHD), Σhexachlorhexane (HCH)) were used in statistical analysis. This study was conducted in three parts.

In the first part, the associations between major groups of POPs and thyroid hormone balances among pregnant women were assessed. Blood samples were collected within a day before delivery from 105 pregnant women of CHECK Panel in 2011. Serum was then analyzed for target POPs along with five thyroid hormones (free and total T3 and T4, and TSH). Several PCBs, such as CB 28, -52, and -118, showed negative associations with T3 or T4. BDE 47 and ΣPBDEs showed significant associations with T3 or T4. For OCPs, ΣDDT and hexachlorobenzene (HCB) were generally associated with the reduction of T3 or T4. While the thyroid hormone levels of all subjects were within the reference range, the levels of exposure to several target POPs were clearly associated with alteration of thyroid hormone balance among pregnant women without any known occupational sources of exposure.

In the second part, the associations between prenatal exposure to major POPs and thyroid hormone levels among newborn infants were investigated (n=104). As thyroid hormone levels in cord blood serum could be influenced by the input of thyroid hormones of maternal origin, thyroid hormone concentrations of the matching mothers at delivery were adjusted. In addition, TSH measured in bloodspot samples of newborn infants on 2 day after birth was used. In cord serum, BDE47, BDE 99, ΣCHD, and p,p'-dichloro-diphenyldichloro-ethylene (DDE) showed significant positive associations with cord blood serum or bloodspot TSH. At the same time, p,p'-DDE and HCB showed negative association with total T3 and T4 in cord serum, respectively. Maternal exposure to β-hexachlorhexane (β-HCH), ΣCHD, ΣDDT, or p,p'-DDE were also associated with neonatal thyroid hormones. Although the sample size was small and the thyroid hormone levels of the subjects were within the reference range, our observation clearly supported endocrine disrupting effects of several POPs among newborn infants at the levels occurring in the general population.

In the third part, the associations between several kinds of maternal POPs exposure and the levels of adipokines in breast milk were investigated (n=50). As the effect marker hormones related to obesity and diabetes, leptin and adiponectin in breast milk were selected. Significant negative association between breast milk leptin concentration and oxy-chlordane (oxyCHD), ∑CHD, BDE 47, or CB 138 levels in maternal serum was observed. P,p-DDT, oxyCHD, tNCHD, ∑CHD, BDE 47, CB 153, or ∑PCB body burden were significantly associated with increased adiponectin concentrations in breast milk samples. Thus, the results of this study provide a line of evidence that POPs at the current level of exposure may link to the alteration of lipid metabolism, which might possibly lead to obesity in later stages of life.

Through a series of cross-sectional studies, it was established that the current levels of exposure to POPs could be associated with the disruption in thyroid hormones and lipid metabolism among pregnant/lactating women or newborn infants. These findings are supported by previous experimental studies, but should be confirmed in prospective birth cohorts with a greater number of subjects for the biological significance. Considering the importance of thyroid hormones and adipokines during gestation and early life stages, health implication of endocrine disruption effects by low level POPs exposure deserves further investigation.
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Graduate School of Public Health (보건대학원)Dept. of Public Health (보건학과)Theses (Ph.D. / Sc.D._보건학과)
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