Previous literature on prenatal phenol exposure and thyroid hormone (TH) alteration is conflicting, and the possible mechanisms of action involved remain unclear. We aimed to examine the association between prenatal phenol exposure and levels of maternal and neonatal THs, as well as the possible role of iodothyronine deiodinase (DIO) gene polymorphisms in this relation. We studied 387 Spanish mother–neonate pairs with measurements of maternal phenols, total triiodothyronine (TT3) and free thyroxine (FT4), maternal and neonatal thyroid-stimulating hormone (TSH), and maternal genotypes for single nucleotide polymorphisms in the DIO1(rs2235544) and DIO2(rs12885300) genes. We implemented multivariate linear and weighted quantile sum (WQS) regressions to examine the association between phenols and THs (including sex-stratified models for neonatal TSH) and investigated effect modification of genotypes in the maternal phenol-TH associations. In single exposure models, we found negative associations between maternal triclosan (TCS) and neonatal TSH (% change [95%CI]: −2.95 [-5.70, -0.11], per twofold phenol increase) – stronger for girls – and less clearly for maternal ethylparaben (EPB) and TSH (−2.27 [-4.55, 0.07]). In phenol mixture models, we found no association with THs. In the genetic interaction models, we found some evidence of effect modification of DIO gene polymorphisms with stronger negative associations between methylparaben (MPB), propylparaben (PPB), butylparaben (BPB) and TT3 as well as bisphenol A (BPA) and FT4 for DIO1(rs2235544)-CC. Stronger inverse associations for genotypes DIO2(rs12885300)-CC and DIO2(rs12885300)-CT and positive ones for DIO2(rs12885300)-TT were also reported for BPA and FT4. In conclusion, we found some evidence of an association between phenols and TSH during pregnancy and at birth in single exposure models, the latter being stronger for girls. Since no association was observed between maternal levels of phenols and TT3 or FT4, the possible role of the genetic background in these associations warrants further investigation.

The abnormality in thyroid hormone modulation in developmental fish, vulnerable to per- and polyfluorinated substances, is of particular concerns for the alternative substances. Juvenile rare minnows, were exposed to chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), the novel alternatives to perfluorooctane sulfonate (PFOS), for 4 weeks followed by 12 weeks of depuration. Half lives were determined to be 33 d, 29 d, and 47 d for total Cl-PFESAs, C8 Cl-PFESA and C10 Cl-PFESA, respectively. Preliminary toxicity test suggested that Cl-PFESAs are moderately toxic to Rare minnow with a LC50 of 20.8 mg/L (nominal concentration） after 96 h of exposure. In the chronic toxicity test, fishes were exposed to Cl-PFESAs at geometric mean measured concentrations of 86.5 μg/L, 162 μg/L and 329 μg/L. In juvenile fishes exposed to Cl-PFESAs for 4 weeks, gene profile sequencing analysis identified 3313 differentially expressed genes, based on which pathways regulating thyroid hormone synthesis and steroid synthesis were enriched. Both whole body total and free 3,5,3′-triiodothyronine (T3) levels were significantly increased. mRNA expression of genes regulating thyroid hormone synthesis (corticotropin-releasing hormone (CRH), thyroid-stimulating hormone (THS), sodium/iodide symporter (NIS), thyroglobulin (TG), and thyroid peroxidase (TPO), transport (transthyretin,TTR), deiodinase (Dio1, Dio2) and receptor (TRα and TRβ) were decreased. Uridinediphosphate glucoronosyl-transferases (UGT1A) gene, regulating THs metabolism, was also decreased. In adult fish, thyroid hormone and genes expression in hypothalamic-pituitary-thyroid axis remained at disturbed levels after 12 weeks of depuration without exposure. Chronic developmental exposure to Cl-PFESAs caused persistent thyroid hormone disrupting effects in fish, highlighting a necessity of comprehensive ecological risk assessment.

Tributyltin is a biocide used in nautical paints, aiming to reduce fouling of barnacles in ships. Despite the fact that many effects of TBT on marine species are known, studies in mammals have been limited, especially those evaluating its effect on the function of the hypothalamus-pituitary-thyroid (HPT) axis. The aim of this study was to investigate the effects of subchronic exposure to TBT on the HPT axis in female rats. Female Wistar rats received vehicle, TBT 200 ng kg−1 BW d−1 or 1000 ng kg−1 BW d−1 orally by gavage for 40 d. Hypothalamus, pituitary, thyroid, liver and blood samples were collected. TBT200 and TBT1000 thyroids showed vacuolated follicular cells, with follicular hypertrophy and hyperplasia. An increase in epithelial height and a decrease in the thyroid follicle and colloid area were observed in TBT1000 rats. Moreover, an increase in the epithelium/colloid area ratio was observed in both TBT groups. Lower TRH mRNA expression was observed in the hypothalami of TBT200 and TBT1000 rats. An increase in Dio1 mRNA levels was observed in the hypothalamus and thyroid in TBT1000 rats only. TSH serum levels were increased in TBT200 rats. In TBT1000 rats, there was a decrease in total T4 serum levels compared to control rats, whereas T3 serum levels did not show significant alterations. We conclude that TBT exposure can promote critical abnormalities in the HPT axis, including changes in TRH mRNA expression and serum TSH and T4 levels, in addition to affecting thyroid morphology. These findings demonstrate that TBT disrupts the HPT axis. Additionally, the changes found in thyroid hormones suggest that TBT may interfere with the peripheral metabolism of these hormones, an idea corroborated by the observed changes in Dio1 mRNA levels. Therefore, TBT exposition might interfere not only with the thyroid axis but also with thyroid hormone metabolism.

Perfluoroalkyl substances (PFASs) are pollutants that tend to accumulate in the environment and organisms. The animal and human studies to date have focused on thyroid function, but the results are inconsistent.A sample of 118 mother-infant pairs was obtained from the Taiwan Birth Panel Study (TBPS). Cord blood PFASs levels were evaluated using the Waters ACQUITY UPLC system coupled with a Waters Quattro Premier XE triple quadrupole mass spectrometer, and cord blood thyroid hormones were assessed using a Roche Analytics E170 modular analyser (Roche Diagnostics, Mannheim, Germany). PFASs concentrations were analysed in the final models to examine the associations between cord blood PFASs levels and thyroid hormone concentrations.The cord blood perfluorooctane sulfonate (PFOS) concentration was negatively associated with the cord blood thyroxine (T4) concentration [per ln unit: adjusted β (95% confidence interval, CI) = −0.458(−0.916, −0.001)]. Moreover, the level of cord blood thyroid stimulating hormone (TSH) was positively associated with the cord blood PFOS concentration [per ln unit: adjusted β (95% confidence interval, CI) = 0.346(0.101, 0.592)]. The sex stratified effects of PFOS on T4 were suggestive of differential effects in high-exposure groups compared with low-exposure group in boys.We found that cord blood thyroid hormone levels are affected by PFASs, with a negative association between T4 and PFOS and a positive association between TSH and PFOS. The causal associations of thyroid hormones and PFASs require further exploration.

To Date, the knowledge on relationship between PCBs/PBDEs exposure and thyroid hormones (THs) levels during pregnancy still needs to be extended. Meanwhile, studies on congener-specific adipose-serum ratios for PCBs/PBDEs were limited. This study reports the levels of PCBs/PBDEs in serum-adipose tissue samples (n = 64) from expectant women living surrounding e-waste recycling sites in Wenling, China. Their concentrations varied from several to hundreds of ng g−1 lipid. Maternal exposure to PCBs was associated with lower TSH during pregnancy, suggesting possible implication for maternal health and fetal development. The compound levels between the adipose tissue and matched serum samples were highly correlated (p < 0.001), generating a predicted adipose-serum partitioning relationship for individual PCB congener and PBDE congener. Molecular characteristics, such as Kow value, molecular weight and molecular volume, may play a key role in the variable partitioning of some compounds between serum and adipose tissue.

The fetus is prenatally exposed to a mixture of organochlorine pesticides (OCPs), mercury (Hg), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and selenium (Se) through maternal seafood consumption in real-life scenario. Prenatal exposure to these contaminants and nutrients has been suggested to affect thyroid hormone (TH) status in newborns, but the potential relationships between them are unclear and the joint effects of the mixture are seldom analyzed. The aim of the study is to investigate the associations of prenatal exposure to a mixture of OCPs, Hg, DHA, EPA and Se with TH parameters in newborns. 228 mother-infant pairs in Shanghai, China were included. We measured 20 OCPs, total Hg, DHA, EPA and Se in cord blood samples as exposure variables. The total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels and the FT3/FT4 ratio in cord serum were determined as outcomes. Using linear regression models, generalized additive models and Bayesian kernel machine regression, we found dose-response relationships of the mixture component with outcomes: among the contaminants, p,p'-DDE was the most important positive predictor of TT3, while HCB was predominantly positively associated with FT3 and the FT3/FT4 ratio, indicating different mechanisms underlying these relationships; among the nutrients, EPA was first found to be positively related to the FT3/FT4 ratio. Additionally, we found suggestive evidence of interactions between p,p'-DDE and HCB on both TT3 and FT3, and EPA by HCB interactions for TT3, FT3 and FT3/FT4 ratio. However, the overall effects of the mixture on thyroid hormone parameters were not significant. Our result suggests that prenatal exposure to p,p’-DDE, HCB and EPA as part of a mixture might affect thyroid function of newborns in independent and interactive ways. The potential biological mechanisms merit further investigation.

Prior human studies have explored effects of phthalate exposures on thyroid function, but the underlying biological mechanisms remain poorly unclear. We aimed to explore the associations between phthalate exposures and thyroid function among a potentially susceptible population such as patients with thyroid nodules, and further to assess the mediating role of oxidative stress. We measured eight phthalate metabolites, three oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F₂α (8-isoPGF₂α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine and three thyroid function biomarkers [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)] in serum among 214 patients with thyroid nodules. Multivariate regression models were applied to assess the associations among urinary phthalate metabolites, oxidative stress and thyroid function biomarkers. The potential mediating role of oxidative stress was explored by mediation analysis. We observed that multiple urinary phthalate metabolites were associated with altered FT4 and increased oxidative stress biomarkers (all FDR-adjusted P ≤ 0.05). Meanwhile, we found that 8-isoPGF₂α was negatively associated with FT3/FT4 among patients with benign thyroid nodules (FDR-adjusted P = 0.08). The mediation analysis indicated that 8-isoPGF₂α mediated the associations of urinary MEHHP and %MEHP with FT3/FT4, with 55.6% and 32.6% proportion of the mediating effects, respectively. Our data suggest that lipid peroxidation may be an intermediate mechanism involved in the effects of certain phthalate exposures on altered thyroid function among patients with benign thyroid nodules.

Prenatal fine particulate matter (PM₂.₅) exposure has been associated with impaired offspring neurodevelopment; however, the association of PM₂.₅ exposure during preconception with offspring’s neurodevelopment and factors responsible for this association are still unclear. This study estimated the associations of PM₂.₅ exposure during preconception and the first trimester with offspring neurodevelopment and evaluated whether maternal thyroid hormones mediate these associations. We recruited 1329 mother-child pairs between 2013 and 2015 in Wuhan, China. PM₂.₅ exposure levels of each woman during the 3 months preconception and the first trimester were estimated using land-use regression models. Offspring neurodevelopment characterized by mental developmental index (MDI) and psychomotor developmental index (PDI) were measured at 24 months of age. Maternal serum levels of free thyroxine (FT3), free triiodothyronine (FT4), and thyroid-stimulating hormone (TSH) during early pregnancy were measured of a subset of the 1329 women (551 women). Generalized estimation equation and general linear regression models were used to estimate the associations between maternal PM₂.₅ exposure, thyroid hormones, and offspring neurodevelopment. After adjusting for potential confounders, we found that either among all participants or the subset, PM₂.₅ exposure during preconception and the first trimester was negatively associated with offspring PDI. Double increment in the first trimester PM₂.₅ exposure was significantly associated with 3.43 and 6.48 points decrease in offspring MDI. In the subset, each doubling of PM₂.₅ exposure during preconception and the first trimester was significantly associated with 7.93 and 8.02 points decrease in maternal FT4 level, respectively. Increased maternal FT4, in turn, was associated with increased PDI (β = 16.69, 95% CI: 5.39, 27.99). About 7.7% (95% CI: 2.0%–19.4%) and 8.6% (95% CI: 3.0%, 22.1%) of the effect of PM₂.₅ exposure during preconception on offspring PDI was mediated through maternal FT4 and the FT4/FT3 ratio, respectively.

Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and new flame retardants (NFRs) are known thyroid hormone (TH) disruptors, but their disrupting mechanisms in humans are not completely understood. In this study, we aimed to explore the disrupting mechanisms of the aforementioned chemicals via examining TH-regulated proteins and gene expression in human serum. Adult participants from an e-waste dismantling (exposed group) and a control region (control group) in South China provided blood samples for the research. Some compounds of PCBs, PBDEs, and NFRs showed strong binding affinity to the thyroid-stimulating hormone (TSH), thyroglobulin, thyroxine-binding globulin (TBG), gene expression of TH receptor α (TRα) and β, and iodothyronine deiodinase I (ID1). The highly exposed individuals had lower levels of TBG, TSH, and expression of TRα, but higher expression of ID1 than those of the control group. The disruption of TH-regulated proteins and gene expression suggested the exertion of different and, at times, even contradictory effects on TH disruption. However, no statistically significant difference was found in the TH levels between the exposed and the control group, implying that the TH disruption induced by these chemicals depends on the combined influence of multiple mechanisms. Gene expression appears to be an effective approach for investigations of TH disruption and the potential health effects.

Prenatal exposure to polychlorinated biphenyl (PCB) is suspected to interfere with fetal development including reproductive and thyroid function and birth outcomes, but published evidence are still sparse. We designed a cross-sectional study to analyze the associations between PCB levels in umbilical cord sera and hormones and birth outcomes of mothers and newborns who are residents from an island. Seven indicator-PCB (PCB-28, 52, 101, 118, 138, 153, 180), and five reproductive hormones including luteotropic hormones (LH), estradiol (E2), testosterone (T), follicle-stimulating hormones (FSH) and anti-Mullerian hormones (AMH), and three thyroid hormones including tri-iodothyronine (T3), tetra-iodothyronine (T4) and thyroid stimulating hormones (TSH) were measured in 106 cord sera specimens. Birth outcomes include birth weight, length, head circumference, and gestational age. Multiple linear regression and quartile regression were used to analyze the associations between PCB and each of the hormones and birth outcomes, adjusting for selected potential confounders. The median value of total PCB in umbilical cord sera was 2.02 μg L−1 (IQR, 1.13–4.64). Several negative associations between PCB exposure and reproductive hormones were found. Among them, the β value of PCB-101 for FSH reached −0.38 (95%CI, −0.69, −0.07; p = 0.02). Moreover, we also found some sex-specific associations i.e. PCB-28 was negatively correlated with LH and T and PCB-118 was negatively correlated with T in male newborns but not in female newborns. The associations between PCB and birth outcomes seem to differ by molecular weight of the PCB congeners i.e. the low-chlorinated PCB congeners were negatively associated with gestational age and head circumference while high-chlorinated PCB congeners were positively associated birth weight and gestational age. In this study, we found that PCB congeners with different molecular weight has different associations with hormones and birth outcomes, and future studies are recommended to investigate underlying mechanisms of these associations.