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.

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.

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.

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.

Organochlorine pesticides (OCPs) had been widely used in agriculture and disease prevention from the 1940s–1960s. Currently, OCPs are raising global concerns due to their associated prevalent contamination and adverse health effects, such as endocrine disruption. Several epidemiological studies have explored the underlying association of OCPs on thyroid hormone (TH) status in adults and newborns, but the results of studies performed on newborns are often inconclusive. This exploratory study was conducted with the purpose of assessing the potential association of the prenatal exposure to OCPs with the concentrations of TH in the cord blood of newborns from China. Cord blood and information on demographic characteristics were collected from 115 newborns between November 2013 and June 2014. The exposure levels of 17 OCPs were measured with a gas chromatography/mass spectrometry, and TH levels including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were detected using electrochemiluminescence immunoassay methods. After adjusting for confounding factors (the age of pregnant mothers, education level, monthly household income, parity, and sex of the newborns), we found marginally significant inverse associations of cord plasma measurements of ∑hexachlorcyclohexanes (∑HCHs), 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene (ρ,ρ′-DDE) and methoxychlor with FT4 levels, but not with FT3 and TSH levels. Moreover, higher cord plasma levels of aldrin, dieldrin, ∑dichlorodiphenyltrichloroethanes (∑DDTs), ∑Drins, and ∑OCPs were found to be related to the increase in cord plasma TSH levels after the adjustment for confounders. The results of this exploratory study indicate that in utero exposure to certain OCPs may affect TH status in newborns, and therefore, pose potential effects on early human development. Further research, with larger sample sizes, should be conducted to confirm these findings.

Exposure to lead(Pb) or cadmium(Cd) has been related to decreasing thyroxine in many previous studies. The underlying mechanisms have not been clarified. Heavy metal-induced thyroid autoimmunity in pregnant women has been found, despite having been rarely explored in the general population.We aimed to determine whether the blood levels of lead(BPb) or cadmium(BCd) related to the levels of sera antibodies to thyroid proteins and thyroid dysfunction in the general population.Our study included 5628 Chinese adults and was based on the 2014 SPECT-China study. Thyroid dysfunction and subclinical thyroid dysfunction were defined by total triiodothyronine (TT3), total thyroxine(TT4) and thyroid stimulating hormone (TSH).Thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies (TGAb), TT3, TT4, and TSH were measured by immunochemiluminometric assays. BPb and BCd levels were tested by atomic absorption spectrometry. Linear and logistic regression models were used to analyze the associations.After adjustment for age, body mass index, smoking status (men only) and drinking status, the natural log(ln) BPb was positively related to the lnTPOAb (B = 0.062, P < 0.05) and to the lnTSH (B = 0.047, P < 0.01) in women. The lnBCd in women was positively related to the lnTGAb (B = 0.046, P < 0.05). In the adjusted logistic regression models, the BCd of women was positively related to their hypothyroid status and TGAb tertiles. The ORs of women in the middle and higher TPOAb tertiles were 1.38 (P < 0.001) and 1.35 (P < 0.001) times greater for every ln-unit increase in BPb, respectively. In men, no continuous correlation was found among variables.In women, BPb and BCd levels were related to higher TSH and hypothyroid status, respectively, suggesting a Pb and Cd induction of sex-biased thyroid autoimmunity.

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.

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.

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 (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.