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.

Perfluoroalkyl substances (PFAS) are a diverse class of manufactured compounds used in a wide range of industrial processes and consumer products and have been detected in human serum worldwide. Previous cross-sectional and cohort studies in humans have suggested exposure to PFAS is associated with a wide array of chronic diseases, including endocrine disruption, developmental health effects, cancer and metabolic changes. We examined the associations between a panel of eight PFAS and indicators of thyroid disruption, kidney function, and body mass index (BMI), all of which were measured at repeated time points (1990–2008) over the course of the study. Participants (N = 210) were selected from the Fernald Community Cohort based on household water supply from a PFAS-contaminated aquifer. In adjusted repeated measures models, we observed several notable associations between serum PFAS and thyroid hormones as well as kidney function as measured by estimated glomerular filtration rate (eGFR). An interquartile (IQR) increase in serum PFOS was associated with a 9.75% (95% CI = 1.72, 18.4) increase in thyroid stimulating hormone. An IQR increase in serum PFNA, PFHxS, and PFDeA was associated with a −1.61% (95% CI = −3.53, −0.59), −2.06% (95% CI = −3.53, −0.59), and −2.20% (95% CI = −4.25, −0.14) change in eGFR, respectively. On the other hand, an IQR increase in serum Me-PFOSA was associated with a 1.53% (95% CI = 0.34, 2.73) increase in eGFR. No significant associations with BMI and serum PFAS were noted. Our findings are in agreement with previous reports that serum PFAS are associated with altered kidney and thyroid function.

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.

Early pregnancy is crucial for fetal growth. Maternal thyroid hormone is critical for fetal growth and can be disturbed under exogenous exposure. However, it's uncertain whether exposure to PM₂.₅ and inorganic constituents during early pregnancy can affect TH and fetal growth. We focused on the associations of early-pregnancy PM₂.₅ and inorganic constituents with fetal growth and maternal THs. PM₂.₅ concentration was estimated using a satellite-based spatiotemporal model. Fetal biparietal diameter (BPD), head circumference (HC), femur length (FL), and humerus length (HL) were measured by ultrasonography at median 15.6, 22.2, and 33.1 gestational weeks. Levels of 28 PM₂.₅ constituents were measured in a sub-group of 329 pregnancies. Maternal serum free thyroxine (fT4), free triiodothyronine, and thyroid-stimulating hormone levels were measured at 14 weeks of gestation. Mixed-effect models and multiple linear regression were applied to evaluate the associations of PM₂.₅ and its constituents with fetal growth measures. Mediation analysis was used to examine the mediating role of the THs. Results showed that each 10 μg/m³ increase in PM₂.₅ was associated with 0.20 mm reductions in BPD (95%CI: 0.33, −0.01), 0.27 mm decreases in FL (95%CI: 0.40, −0.13), and 0.36 decreases in HL (95%CI: 0.49, −0.23). Per 10 μg/m³ increment in PM₂.₅ was correlated with 5.82% decreases in the fT4 level (95% CI: 8.61%, −2.96%). FT4 accounted for 14.3% of PM₂.₅ exposure-induced change in BPD at first follow-up. Al (β = −2.91, 95%CI: 5.17, −0.66), Si (β = −1.20, 95%CI: 2.22, −0.19), K (β = −3.09, 95%CI: 5.41, −0.77), Mn (β = −47.20, 95%CI: 83.68, −10.79) and Zn (β = −3.02, 95%CI: 5.55, −0.49) were associated with decreased fetal BPD, especially in first follow-up. Zn (β = −38.12%, 95% CI: 58.52%, −8.61%) was also associated with decreased fT4 levels. Overall, early pregnancy exposure to PM₂.₅ and its constituents was associated with fetal growth restriction and decreased maternal fT4 levels might mediate the effect of PM₂.₅.

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.

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.

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.

The last decades have seen the increasing prevalence of thyroid disorders. These augmentations could be the consequence of the increasing contamination of the environment by chemicals that may disrupt the thyroid function. Indeed, in vitro studies have shown that many chemicals contaminating our environment and highlighted in human serum, are able to interfere with the thyroid function. Given the crucial importance of thyroid hormones on neurodevelopment in fetus and newborns, the influence of these pollutants on newborn thyroid homeostasis is a major health concern. Unfortunately, the overall evidence for a deleterious influence of environmental pollutants on thyroid remains poorly studied. Therefore, we assessed the contamination by polychlorinated biphenyls (PCBs), organochlorine pesticides and perfluorinated compounds (PFC) in 221 cord blood samples collected in Belgium between 2013 and 2016. Our results showed that compared to previous studies performed on newborns recruited in Belgium during the two last decades, the present pollutant contamination is declining. Multivariate statistical analyses pointed out a decrease of thyroid stimulating hormone (TSH) level in male newborns with detectable level of 4,4′- dichlorodiphenyldichloroethylene (4,4′-DDE) in comparison with those with no detectable level (p = 0.025). We also highlighted a negative association between perfluorononanoic acid (PFNA) concentration and TSH in male newborns (p = 0.018). Logistic regression showed increased odds ratio for presentation of hypothyroid in mother for each one unit augmentation of log natural concentration of PFOA (OR = 2.30, [1.18–4.5]) and PFOS (OR = 2.03 [1.08–3.83]). Our findings showed that the residual contamination by PFCs and organochlorine pollutants in cord blood are correlated with thyroid hormone in the newborns and the risk of hypothyroid in mothers.

Hexachloronaphthalene (HxCN) is one of the most toxic and most bioaccumulative congeners of polychlorinated naphthalenes (PCNs) known to be present in animal and human adipose tissue. Unfortunately, little data is available regarding the negative effect of PCNs on endocrine function. The aim of the study was to investigate the direct influence of subacute (two and four-week) and subchronic (13-week) daily oral exposure of female rats to 30, 100 and 300 μg kg b.w.⁻¹ HxCN on ovarian, thyroid function and neurotransmitters level. The levels of selected sex hormones (progesterone: P and estradiol: E2) in the serum and uterus, regularity of estrous cycle, levels of thyroid hormones (fT3 and fT4), TSH, γ-aminobutyric acid and glutamate levels in selected brain areas and the activity of CYP1A1 and CYP2B in the liver were examined. Estrogenic action (elevated E2 concentration in the uterus and serum) was observed only after subacute exposure, and antiestrogenic activity (decreased E2 level and uterus weight) after 13 weeks administration of 300 μg kg b.w.⁻¹ day⁻¹. Subchronic administration of HxCN significantly lengthens the estrous cycle, by up to almost 50%, and increases the number of irregular cycles. In addition, increased TSH and decreased fT4 serum levels were observed after all doses and durations of exposure to HxCN. Only subacute exposure led to a significant decrease in the level of examined neurotransmitters in all analyzed structures. Additionally, exposure to low doses of HxCN appears to lead to strong induction of CYP1A1 in a liver. It can be hypothesized that HxCN produces effects which are very similar to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds (DLCs), particularly concerning endocrine and estrous cyclicity disorders. Therefore, HxCN exposure may exert unexpected effects on female fecundity among the general population.

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.