Association between Several Persistent Organic Pollutants and Thyroid Hormone Levels in Cord Blood Serum and Bloodspot of the Newborn Infants of Korea

<div><p>Current knowledge on adverse endocrine disruption effects of persistent organic pollutants (POPs) among newborn infants is limited and often controversial. To investigate the associations between prenatal exposure to major POPs and thyroid hormone levels among newborn infants, both cord serum or maternal serum concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) were compared with five thyroid hormones in cord serum of newborn infants as well as TSH in bloodspot collected at 2 day after birth (n=104). Since cord serum thyroid hormones could be affected by those of mothers, thyroid hormone concentrations of the matching mothers at delivery were adjusted. In cord serum, BDE-47, -99, and Σchlordane (CHD) showed significant positive associations with cord or bloodspot TSH. At the same time, <i>p</i>,<i>p'</i>-dichlorodiphenyldichloroethylene (<i>p</i>,<i>p'</i>-DDE) and hexachlorbenzene (HCB) showed negative associations with total T3 and total T4 in cord serum, respectively. Maternal exposure to <i>β</i>-hexachlorhexane (<i>β</i>-HCH), ΣCHD, ΣDDT, or <i>p</i>,<i>p'</i>-DDE were also associated with neonatal thyroid hormones. Although the sample size is small and the thyroid hormone levels of the subjects were within the reference range, our observation supports thyroid disrupting potential of several POPs among newborn infants, at the levels occurring in the general population. Considering the importance of thyroid hormones during gestation and early life stages, health implication of thyroid hormone effects by low level POPs exposure deserves further follow up investigations.</p></div

Associations between POPs concentrations in maternal blood and thyroid hormone levels in cord blood serum or in bloodspot of newborn infant population in Korea (n = 104).

<p>Signs * and ^ indicate statistical significance of regression parameter at p<0.05, and 0.1, respectively. All POPs concentrations and thyroid hormone levels were natural log—transformed. Results of association regarding free T3, total T3, free T4, total T4, and TSH were adjusted for age, gestation period, mode of delivery, parity, pre-pregnancy BMI, smoking status during pregnancy, and maternal weight gain during pregnancy. While infant sex was added as covariate and smoking status was removed for analysis of bloodspot TSH. Chemicals that were detected > = 75% of the population at concentrations greater than the limit of quantification, a proxy value of ‘limit of quantification divided by square root 2’ was used. For chemicals that were detected in <75% but > = 60%, statistical analysis was conducted with detected values only. Such chemicals are indicated by ‘+’. Since BDE-99 were detected below 60% in maternal serum samples, they were not statistically analyzed.</p><p>Associations between POPs concentrations in maternal blood and thyroid hormone levels in cord blood serum or in bloodspot of newborn infant population in Korea (n = 104).</p

Characteristics of the study population.

<p>^a Normal spontaneous vaginal delivery.</p><p>^b Caesarean section.</p><p>^c Bloodspot TSH was measured from bloodspot samples collected at day 2–7 post-partum. Most newborn babies were collected for bloodspot on day 2 (within 48 hrs) post-partum, but 3 and 2 infants were collected on day 5 and 7 post-partum, respectively.</p><p>Characteristics of the study population.</p

Associations between serum POPs concentrations and thyroid hormones in the sensitivity analysis.

<p>Signs * and ^ indicate statistical significance of regression parameter (β) at p<0.05, and 0.1, respectively. ‘CI’ confidence interval; ‘fT3’ free T3; ‘TT3’ total T3; ‘fT4’ free T4. For the calculation of association, two or more independent variables that were determined as significant predictors to a given thyroid hormone, and at the same time were correlated each other, were added in the multiple regression analysis, in order to identify major predictors. In the regression model, interaction terms between the selected POPs were not included.</p><p>Associations between serum POPs concentrations and thyroid hormones in the sensitivity analysis.</p

Associations between prenatal POPs concentrations in either maternal or cord blood and thyroid hormone levels of newborn infants.

<p>‘-’ no association;</p><p>‘↑’ positive association;</p><p>‘↓’ negative association (p<0.05);</p><p>Blank cell means data not available. ‘fT3’ free T3; ‘TT3’ total T3; ‘fT4’ free T4; ‘TT4’ total T4. In the present study, cord thyroid hormone levels were adjusted with maternal thyroid hormone levels in the model. Unless otherwise noted, all thyroid hormone measurements were from cord blood or cord serum. ‘s’ indicates the measurement in bloodspot of newborn infant.</p><p>Associations between prenatal POPs concentrations in either maternal or cord blood and thyroid hormone levels of newborn infants.</p

Association between Several Persistent Organic Pollutants in Serum and Adipokine Levels in Breast Milk among Lactating Women of Korea

Exposure to several persistent organic pollutants (POPs) has been linked to alteration of lipid metabolism. Adipokines, such as leptin and adiponectin, are hormones that play roles in lipid metabolism, and have been suggested as markers of health effects that may lead to obesity. To date, only serum adipokines have been associated with POPs exposure. In the present study, for the first time, the associations between leptin and adiponectin in breast milk, and several POPs in serum were investigated among 82 lactating Korean women between 25 and 46 years of age. Breast milk adipokines are important because adipokine intake of infant through breastfeeding may influence the growth of infants. The median concentrations of leptin and adiponectin in skimmed milk of the Korean lactating women were 17.9 ng/L and 16.5 μg/L, respectively. Leptin concentrations in breast milk were negatively associated with ∑hexachlorohexane (HCH), oxychlordane, ∑chlordane, or 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB 153) levels in maternal serum. Linear relationships between adiponectin and POPs concentrations were not observed, however, nonmonotonic relationship which showed generally positive associations was suggested for <i>p</i>,<i>p</i>′-dichlorodiphenyltrichloroethane (DDT) and ∑chlordane in quartile analysis. Our observations show that POPs at the current level of exposure may be associated with the alteration of lipid metabolism among lactating women. Implication of adipokine transfer to breastfed infants is of concern and deserves further investigation

Myeloid dendritic cells (CD11b⁺CD11c⁺) are increased in TDLN and are required for tumor regression.

<p>(A) C57BL/6 mice were challenged with 1×10⁶ MB49 on day 0 and treated with Val-boroPro (closed bars) or saline (open bars) during week one (n = 4/group). Tumor-draining lymph nodes were harvested and analyzed by flow cytometry on day 7 (p<0.05, Mann-Whitney) (B) C57BL/6 mice were inoculated with 10⁶ MB49 and injected with clodronate IP (0.1 mL/10 g body weight) every other day from day –1 to 9 following tumor inoculation. Control groups were injected with empty lysosomes or saline (sham). Val-boroPro was administered orally for 1 week (days 3–7). Survival was significantly different in Val-boroPro treated mice given clodronate (thick solid line) compared to those treated with Val-boro-Pro and given empty lysosomes (gray solid line) (*p<0.05, Logrank test, n = 5/group). (C) CD11c-diphtheria toxin (DT) chimeric mice were generated by transplanting bone marrow from CD11c-DT transgenic mice into lethally irradiated C57BL/6 recipients (n = 5/group). Female chimeras were inoculated with 10⁶ MB49 on day 0 and treated with Val-boroPro or saline during week one (days 3–7) with or without IP injections of DT (8 ng/1 g body weight) every other day from day –1 to 9. Tumor volumes were significantly larger in Val-boroPro treated chimeric mice receiving DT (closed circles) compared to Val-boro-Pro treated chimeric mice receiving saline (closed squares) (p<0.001 for all timepoints beyond day 10). Tumor volumes were not statistically different between saline treated (open squares) and DT treated (open circles) chimerics not treated with Val-boroPro. Experiments displayed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058860#pone-0058860-g007" target="_blank">Figures 7A–C</a> were each conducted twice.</p

Characteristics and Mobile Phone Use Patterns of Children in 2008 to 2010, Korea, the CHEER study.

<p>CHEER, Children’s Health and Environmental Health Research, ADHD, Attention Deficit Hyperactivity Disorder. 1 USD equals approximately 1,084.5 KRW as of 8/9/2011.</p>*<p>Among children who owned a mobile phone.</p

Antitumor activity with Val-boroPro is associated with increased trafficking of DCs.

<p>(A–B) B6CD45.1 congenic mice were treated with 20 µg Val-boroPro for three days, and CD11c⁺ cells from spleens and LNs were magnetic bead purified and injected at a dose of 5×10⁶ into lateral tarsals of C57BL/6 (CD45.2⁺) recipients. Immediately following CD11c⁺ cell injection, recipients were treated with Val-boroPro or saline (n = 3/group). Popliteal lymph nodes were harvested 15 hours following Val-boroPro treatment for flow cytometric analysis. (A) Representative dot plots. (B) Bar graph showing statistically more CD45.1⁺ adoptive transferred DCs in the popliteal LN in recipients of DCs from Val-boroPro treated donors also receiving a single injection of Val-boroPro compared to all other group (*p<0.05, **p<0.01, Mann-Whitney). (C) Purified CD11c⁺ cells from Val-boroPro treated GFP⁺ mice were injected intratumorally into established MB49 tumors. Mice were treated immediately thereafter with one dose of Val-boroPro (n = 3/group). Tumor-draining inguinal lymph nodes were harvested 15 hours later and imaged by fluorescent microscopy. Representative lymph nodes from mice receiving CD11c⁺ cells from Val-boroPro treated donors and Val-boroPro post injection. Experiments displayed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058860#pone-0058860-g008" target="_blank">Figures 8A–C</a> were conducted 2 times.</p

Changes in ADHD symptoms according to the change in mobile phone use for voice calls and playing game over 2 years.

<p>Numbers in parentheses are the number of subjects in the corresponding group.</p