Testosterone and persistent organic pollutants in East Greenland male polar bears (Ursus maritimus).

Legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) are chemicals that undergo long-range transport to the Arctic. These chemicals possess endocrine disruptive properties raising concerns for development and reproduction. Here, we report the relationship between concentrations of testosterone (T) and persistent organic pollutant (POPs) in 40 East Greenland male polar bears (Ursus maritimus) sampled during January to September 1999-2001. The mean ± standard concentrations of blood T were 0.31 ± 0.49 (mean ± SD) ng/mL in juveniles/subadults (n = 22) and 3.58 ± 7.45 ng/mL in adults (n = 18). The ∑POP concentrations (mean ± SD) in adipose tissue were 8139 ± 2990 ng/g lipid weight (lw) in juveniles/subadults and 11,037 ± 3950 ng/g lw in adult males, respectively, of which Σpolychlorinated biphenyls (ΣPCBs) were found in highest concentrations. The variation in T concentrations explained by sampling date (season), biometrics and adipose tissue POP concentrations was explored using redundancy analysis (RDA). The results showed that age, body length, and adipose lipid content in adult males contributed (p = 0.02) to the variation in POP concentrations. However, although some significant relationships between individual organochlorine contaminants and T concentrations in both juveniles/subadults and adult polar bears were identified, no significant relationships (p = 0.32) between T and POP concentrations were identified by the RDAs. Our results suggest that confounders such as biometrics and reproductive status may mask the endocrine disruptive effects that POPs have on blood T levels in male polar bears, demonstrating why it can be difficult to detect effects on wildlife populations.

Evaluation of Maternal Exposure to PM2.5 and Its Components on Maternal and Neonatal Thyroid Function and Birth Weight: A Cohort Study.

Background: Particulate matter (PM) air pollution is an environmental risk to public health. The prevalence of thyroid disease during pregnancy has increased rapidly in recent decades, but the available data on the relationships among air pollution, thyroid function, and birth outcomes in pregnant women, particularly in China, are scarce. We aimed to evaluate the association between maternal exposure to PM2.5 and its components and maternal and neonatal thyroid function and to investigate whether thyroid function acts as a mediator between air pollution and birth weight. Methods: In this prospective birth cohort study, the levels of maternal exposure to PM2.5 and its components during the first trimester were assessed in 433 pregnant women in Nanjing, China, enrolled during 2014-2015. We evaluated the levels of maternal exposure to PM2.5 and its six main constituents-organic matter (OM), black carbon (BC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and soil dust-using the V4.CH.02 product of the Dalhousie University Atmospheric Composition Analysis Group. The maternal serum-free thyroxine (fT4), thyrotropin (TSH), and thyroid peroxidase antibody (TPOAb) levels during the second trimester were measured through electrochemiluminescent microparticle immunoassays. The neonatal TSH levels were detected using an AutoDELFIA Neonatal TSH kit within 72 hours after birth, and the birth weight Z-score of each newborn was estimated. Results: Higher exposure to maternal PM2.5 and some components (BC and NH4+) decreased the maternal fT4 level (p < 0.05), and the birth weight Z-score was decreased (p < 0.05) by higher exposure to maternal PM2.5 and some components (OM, BC, NO3-, and NH4+). A mediation analysis clarified that the maternal fT4 levels explained 15.9%, 18.4%, and 20.9% of the associations of maternal PM2.5, BC, and NH4+ exposure with the birth weight Z-score, respectively (p < 0.05). After additional sensitivity analyses including only nonpreterm participants (n = 418) and non-TPOAb-positive participants (n = 415), the models remained stable. Conclusions: Our results suggest an inverse association between maternal exposure to PM2.5 and its components and the maternal fT4 levels. Maternal fT4 might act as a mediator between exposure to PM2.5 and its components and birth weight.

Iodine Intake is Associated with Thyroid Function in Mild to Moderately Iodine Deficient Pregnant Women.

BACKGROUND: Studies indicate that mild to moderate iodine deficiency in pregnancy may have a long-term negative impact on child neurodevelopment. These effects are likely mediated via changes in maternal thyroid function, since iodine is essential for the production of thyroid hormones. However, the impact of iodine availability on thyroid function during pregnancy and on thyroid function reference ranges are understudied. The aim of this study was to investigate the association between iodine intake and thyroid function during pregnancy. DESIGN: In a population-based pregnancy cohort including 2910 pregnant women participating in The Norwegian Mother and Child Cohort Study, we explored cross sectional associations of maternal iodine intake measured (1) by a food frequency questionnaire and (2) as iodine concentration in a spot urine sample, with plasma thyroid hormones and antibodies. RESULTS: Biological samples were collected in mean gestational week 18.5 (standard deviation 1.3) and diet was assessed in gestational week 22. Median iodine intake from food was 121 µg/day (interquartile range 90, 160), and 40% reported use of iodine-containing supplements in pregnancy. Median urinary iodine concentration (UIC) was 59 µg/L among those who did not use supplements and 98 µg/L in the women reporting current use at the time of sampling, indicating mild to moderate iodine deficiency in both groups. Iodine intake as measured by the food frequency questionnaire was not associated with the outcome measures, while UIC was inversely associated with FT3 (p = 0.002) and FT4 (p < 0.001). Introduction of an iodine-containing supplement after gestational week 12 was associated with indications of lower thyroid hormone production (lower FT4, p = 0.027, and nonsignificantly lower FT3, p = 0.17). The 2.5th and 97.5th percentiles of TSH, FT4, and FT3 were not significantly different by groups defined by calculated iodine intake or by UIC. CONCLUSION: The results indicate that mild to moderate iodine deficiency affect thyroid function in pregnancy. However, the differences were small, suggesting that normal reference ranges can be determined based on data also from mildly iodine deficient populations, but this needs to be further studied. Introducing an iodine-containing supplement might temporarily inhibit thyroid hormone production and/or release.

Maternal air pollution exposure and preterm birth in Wuxi, China: Effect modification by maternal age.

BACKGROUND: Numerous studies have investigated prenatal air pollution and shown that air pollutants have adverse effect on birth outcomes. However, which trimester was the most sensitive and whether the effect was related to maternal age is still ambiguous. OBJECTIVES: This study aims to explore the association between maternal air pollution exposure during pregnancy and preterm birth, and if this relationship is modified by maternal age. METHODS: In this retrospective cohort study, we examine the causal relationship of prenatal exposure to air pollutants including particulate matters, which are less than 10 µm (PM10), and ozone (O3), which is one of the gaseous pollutants, on preterm birth by gestational age. A total of 6693 pregnant women were recruited from Wuxi Maternal and Child Health Care Hospital. The participants were dichotomized into child-bearing age group (< 35 years old) and advanced age group (> = 35 years old) in order to analyze the effect modification by maternal age. Logistic and linear regression models were performed to assess the risk for preterm birth (gestational age < 37 weeks) caused by prenatal air pollution exposure. RESULTS: With adjustment for covariates, the highest level of PM10 exposure significantly increased the risk of preterm birth by 1.42-fold (95% CI: 1.10, 1.85) compared those with the lowest level in the second trimester. Trimester-specific PM10 exposure was positively associated with gestational age, whereas O3 exposure was associated with gestational age in the early pregnancy. When stratified by maternal age, PM10 exposure was significantly associated with an increased risk of preterm birth only in the advanced age group during pregnancy (OR:2.15, 95% CI: 1.13, 4.07). The results suggested that PM10 exposure associated with preterm birth was modified by advanced maternal age (OR interaction = 2.00, 95% CI: 1.02, 3.91, Pinteraction = 0.032). CONCLUSION: Prenatal air pollution exposure would increase risk of preterm birth and reduced gestational age. Thus, more attention should be paid to the effects of ambient air pollution exposure on preterm birth especially in pregnant women with advanced maternal age.

Effects of Sample Handling and Analytical Procedures on Thyroid Hormone Concentrations in Pregnant Women's Plasma.

BACKGROUND: Maternal thyroid function is a critical mediator of fetal brain development. Pregnancy-related physiologic changes and handling conditions of blood samples may influence thyroid hormone biomarkers. We investigated the reliability of thyroid hormone biomarkers in plasma of pregnant women under various handling conditions. METHODS: We enrolled 17 pregnant women; collected serum and plasma were immediately frozen. Additional plasma aliquots were subjected to different handling conditions before the analysis of thyroid biomarkers: storage at room temperature for 24 or 48 hours before freezing and an extra freeze-thaw cycle. We estimated free thyroid hormone indices in plasma based on T3 uptake. RESULTS: High correlations between plasma and serum (>0.94) and intraclass correlation coefficients for plasma handling conditions (0.96 to 1.00) indicated excellent reliability for all thyroid hormone biomarkers. CONCLUSION: Delayed freezing and freeze-thaw cycles did not affect reliability of biomarkers of thyroid function in plasma during pregnancy. See video abstract at, http://links.lww.com/EDE/B180.

Thyroid hormones and deiodinase activity in plasma and tissues in relation to high levels of organohalogen contaminants in East Greenland polar bears (Ursus maritimus).

Previous studies have shown relationships between organohalogen contaminants (OHCs) and circulating levels of thyroid hormones (THs) in arctic wildlife. However, there is a lack of knowledge concerning the possible functional effects of OHCs on TH status in target tissues for TH-dependent activity. The relationships between circulating (plasma) levels of OHCs and various TH variables in plasma as well as in liver, muscle and kidney tissues from East Greenland sub-adult polar bears (Ursus maritimus) sampled in 2011 (n=7) were therefore investigated. The TH variables included 3.3',5.5'-tetraiodothyronine or thyroxine (T4), 3.3',5-triiodothyronine (T3) and type 1 (D1) and type 2 (D2) deiodinase activities. Principal component analysis (PCA) combined with correlation analyses demonstrated negative relationships between individual polychlorinated biphenyls (PCBs) and their hydroxylated (OH-) metabolites and T4 in both plasma and muscle. There were both positive and negative relationships between individual OHCs and D1 and D2 activities in muscle, liver and kidney tissues. In general, PCBs, OH-PCBs and polybrominated dipehenyl ethers (PBDEs) were positively correlated to D1 and D2 activities, whereas organochlorine pesticides and byproducts (OCPs) were negatively associated with D1 and D2 activities. These results support the hypothesis that OHCs can affect TH status and action in the target tissues of polar bears. TH levels and deiodinase activities in target tissues can be sensitive endpoints for exposure of TH-disrupting compounds in arctic wildlife, and thus, tissue-specific responses in target organs should be further considered when assessing TH disruption in wildlife studies.

Levels and patterns of hydroxylated polychlorinated biphenyls (OH-PCBs) and their associations with thyroid hormones in hooded seal (Cystophora cristata) mother-pup pairs.

Blood (plasma/serum) samples from 14 adult female and their pups (1-4 days old) captured in the West Ice, east of Greenland were analysed for concentrations of total and free thyroxine and triiodothyronine (TT4, FT4, TT3, FT3), and hydroxylated polychlorinated biphenyls (OH-PCBs). The levels of all thyroid hormones (THs) were significantly higher in pups than in mothers. Sum OH-PCB levels (ΣOH-PCBs: 4-OH-CB107, 3'-OH-CB138, 4-OH-CB146, 4'-OH-CB172, 4-OH-CB187) were significantly higher in mothers (3.98 ± 1.55 pmol/g; 1.40 ± 0.54 ng/g wet weight) as compared to pups (1.95 ± 0.78 pmol/g; 0.68 ± 0.28 ng/g wet weight). Plasma levels of TT4 and FT4 in mothers increased as a function of pup age, as did levels of individual OH-PCBs in both mothers and pups. The pattern of OH-PCBs in the pups was similar to their mothers. We suggest that OH-PCBs found in pups are transferred from their mothers during gestation and that the transfer also continues after parturition via milk. Principal component analysis (PCA) showed that in pups, 4-OH-CB107 and 3'-OH-CB138 were negatively associated with FT4:FT3 and TT3:FT3 ratios, respectively. These relationships were confirmed by partial correlation analysis correcting for pup age. PCA suggested that 4'-OH-CB172 and 4-OH-CB187 were negatively associated with TT3 in mothers. However, this was not confirmed by correlation tests. Although statistical relationships should be interpreted with caution, the study indicates that young developing seals are more sensitive compared to adults with respect to TH-related effects of OH-PCBs.