International audience | Mice were exposed to a low dose of the model thyroid hormone disruptor, propylthiouracil. Although this had only a modest effect on maternal thyroid hormones production, postnatal analysis of the pups’ plasma by mass spectrometry and the brain striatum by RNA sequencing gave evidence of low lasting changes that could reflect an adverse effect on neurodevelopment. Overall, these methods proved to be sensitive enough to detect minor disruptions of thyroid hormone signalling in vivo.

International audience | Polycyclic aromatic hydrocarbons (PAHs) have been shown to influence endogenous hormones levels in animal models, but little is known about the effects of their mixtures. For hormone measurements, hair analysis is a promising approach to provide information on long-term status of hormones. Herein we used hair analysis to assess the combined effects of 13 PAHs on steroid and thyroid hormones levels in a rat model. The PAH mixture was administered orally three times per week to female rats at doses of 0, 10, 20, 40, 80, 200, 400 and 800 μg/kg of body weight for each compound over a 90-day exposure period. Fourteen out of 36 analyzed hormones were detected in rat hair, including pregnenolone (P5), 17α-hydroxyprogesterone (17-OHP4), corticosterone (CORT), dehydroepiandrosterone (DHEA), androstenedione (AD), 3,3'-diiodo-L-thyronine (T2), 3,3',5-triiodo-L-thyronine (T3), and 3,5,3',5'-triiodo-L-thyronine (T4). The PAH mixture significantly elevated P5 and DHEA levels at the doses of 200 and 400 μg/kg but reduced T2 and T3 levels at the highest dose as compared to the control. While P5, DHEA, 17-OHP4 and AD concentrations exhibited inverted U-shaped dose responses, T2, T3 and T4 concentrations exhibited inverse linear dose responses, which are further confirmed by their relationships with hair hydroxylated PAHs (OH-PAHs) concentrations. Likewise, there were significant nonmonotonic relationships of hormone molar ratios (e.g., AD/17-OHP4 and DHEA/CORT ratios) with exposure intensity and OH-PAHs. Overall, our results demonstrate the capability of PAH mixtures to interfere with steroid and thyroid hormones in female rats.

International audience | Polycyclic aromatic hydrocarbons (PAHs) have been shown to influence endogenous hormones levels in animal models, but little is known about the effects of their mixtures. For hormone measurements, hair analysis is a promising approach to provide information on long-term status of hormones. Herein we used hair analysis to assess the combined effects of 13 PAHs on steroid and thyroid hormones levels in a rat model. The PAH mixture was administered orally three times per week to female rats at doses of 0, 10, 20, 40, 80, 200, 400 and 800 μg/kg of body weight for each compound over a 90-day exposure period. Fourteen out of 36 analyzed hormones were detected in rat hair, including pregnenolone (P5), 17α-hydroxyprogesterone (17-OHP4), corticosterone (CORT), dehydroepiandrosterone (DHEA), androstenedione (AD), 3,3'-diiodo-L-thyronine (T2), 3,3',5-triiodo-L-thyronine (T3), and 3,5,3',5'-triiodo-L-thyronine (T4). The PAH mixture significantly elevated P5 and DHEA levels at the doses of 200 and 400 μg/kg but reduced T2 and T3 levels at the highest dose as compared to the control. While P5, DHEA, 17-OHP4 and AD concentrations exhibited inverted U-shaped dose responses, T2, T3 and T4 concentrations exhibited inverse linear dose responses, which are further confirmed by their relationships with hair hydroxylated PAHs (OH-PAHs) concentrations. Likewise, there were significant nonmonotonic relationships of hormone molar ratios (e.g., AD/17-OHP4 and DHEA/CORT ratios) with exposure intensity and OH-PAHs. Overall, our results demonstrate the capability of PAH mixtures to interfere with steroid and thyroid hormones in female rats.

International audience | Triazoles belong to a family of fungicides that are ubiquitous in agroecosystems due to their widespread use in crops. Despite their efficiency in controlling fungal diseases, triazoles are also suspected to affect non-target vertebrate species through the disruption of key physiological mechanisms. Most studies so far have focused on aquatic animal models, and the potential impact of triazoles on terrestrial vertebrates has been overlooked despite their relevance as sentinel species of contaminated agroecosystems. Here, we examined the impact of tebuconazole on the thyroid endocrine axis, associated phenotypic traits (plumage quality and body condition) and sperm quality in wild-caught house sparrows (Passer domesticus). We experimentally exposed house sparrows to realistic concentrations of tebuconazole under controlled conditions and tested the impact of this exposure on the levels of thyroid hormones (T3 and T4), feather quality (size and density), body condition and sperm morphology. We found that exposure to tebuconazole caused a significant decrease in T4 levels, suggesting that this azole affects the thyroid endocrine axis, although T3 levels did not differ between control and exposed sparrows. Importantly, we also found that exposed females had an altered plumage structure (larger but less dense feathers) relative to control females. The impact of tebuconazole on body condition was dependent on the duration of exposure and the sex of individuals. Finally, we did not show any effect of exposure to tebuconazole on sperm morphology. Our study demonstrates for the first time that exposure to tebuconazole can alter the thyroid axis of wild birds, impact their plumage quality and potentially affect their body condition. Further endocrine and transcriptomic studies are now needed not only to understand the underlying mechanistic effects of tebuconazole on these variables, but also to further investigate their ultimate consequences on performance (i.e. reproduction and survival).

International audience | Triazoles belong to a family of fungicides that are ubiquitous in agroecosystems due to their widespread use in crops. Despite their efficiency in controlling fungal diseases, triazoles are also suspected to affect non-target vertebrate species through the disruption of key physiological mechanisms. Most studies so far have focused on aquatic animal models, and the potential impact of triazoles on terrestrial vertebrates has been overlooked despite their relevance as sentinel species of contaminated agroecosystems. Here, we examined the impact of tebuconazole on the thyroid endocrine axis, associated phenotypic traits (plumage quality and body condition) and sperm quality in wild-caught house sparrows (Passer domesticus). We experimentally exposed house sparrows to realistic concentrations of tebuconazole under controlled conditions and tested the impact of this exposure on the levels of thyroid hormones (T3 and T4), feather quality (size and density), body condition and sperm morphology. We found that exposure to tebuconazole caused a significant decrease in T4 levels, suggesting that this azole affects the thyroid endocrine axis, although T3 levels did not differ between control and exposed sparrows. Importantly, we also found that exposed females had an altered plumage structure (larger but less dense feathers) relative to control females. The impact of tebuconazole on body condition was dependent on the duration of exposure and the sex of individuals. Finally, we did not show any effect of exposure to tebuconazole on sperm morphology. Our study demonstrates for the first time that exposure to tebuconazole can alter the thyroid axis of wild birds, impact their plumage quality and potentially affect their body condition. Further endocrine and transcriptomic studies are now needed not only to understand the underlying mechanistic effects of tebuconazole on these variables, but also to further investigate their ultimate consequences on performance (i.e. reproduction and survival).

Although the coexistence of heavy metals and environmental hormones always occur in aquatic environment, the information of the combined impacts remains unclear. To explore the multi-generational toxicity of cadmium (Cd) and tributyltin (TBT), adult zebrafish (Danio rerio) (F0) were exposed to different treated groups (100 ng/l Cd, 100 ng/l TBT and their mixture) for 90 d, with their offspring (F1 and F2) subsequently reared in the same exposure solutions corresponding to their parents. Both developmental neurotoxicity and thyroid disturbances were examined in the three (F0, F1, and F2) generations. Our results showed that co-exposure to Cd and TBT induced the developmental neurotoxicity in F1 and F2 generations, reflected by the significant lower levels of neurotransmitters (dopamine and serotonin) and the inhibited acetylcholinesterase (AChE) activities. And the thyroid endocrine disruption were observed in the two-generations larval offspring by parental exposure to Cd and/or TBT, including the significantly decreasing levels of thyroid hormones and the down-regulated the expression of genes involved in the hypothalamus-pituitary-thyroid axis, compared to the control. Additional, the embryonic toxicity and growth inhibition were also determined in the fish larvae. Overall, this study examined the impacts of parental co-exposure to Cd and TBT, with regard to developmental inhibition, nervous system damage and endocrine disruption, which highlighted that co-exposure influences are complicated and need to be considered for accurate environmental risk assessment.

As a widely used organotin acaricide nowadays, azocyclotin (ACT) could induce thyroidal endocrine disruption in fishes and amphibians, but its dominant disrupting mode remains unknown. In this study, zebrafish were firstly exposed to ACT (0.18–0.36 ng/mL) from 2 hpf (hours post fertilization) to 30 dpf (days post fertilization), and a series of developmental toxicological endpoints and thyroid hormones were measured. Result showed that no developmental toxicity to zebrafish was found in 0.18 and 0.24 ng/mL groups except decreased body weight (30 dpf, 0.24 ng/mL). However, exposed to 0.36 ng/mL ACT led to reductions in heartbeat (48 hpf), hatching rate (72 hpf) and bodyweight (30 dpf). General tendencies of decreases in free T3 but increases in free T4 and reductions in ratio of free T3/T4 were also found, inferring that type II deiodinase (Dio2) was repressed. This inference was confirmed by Western analysis that Dio2 expression reduced by 42.7% after 0.36 ng/mL ACT treatment. Moreover, RNA-Seq analysis implied that exposed to 0.36 ng/mL ACT altered the genome-wide gene expression profiles of zebrafish. Totally 5660 genes (involving 3154 down-regulated and 2596 up-regulated genes) were differentially expressed, and 13 deferentially expressed genes including down-regulated dio2 were significantly enriched in thyroid hormone signaling pathway. Subsequently, an in vitro thyroid receptor-reporter gene assay using GH3 cells was performed to further explore the potential disrupting mechanism. Result showed that luciferase activity slightly increased after exposure to ACT alone or ACT combined with low level T3, but was suppressed when combined with high level T3. It indicted there probably existed a competitive relationship in some extent between ACT and T3 in vivo. Overall, the present study provided preliminary evidences that long-term exposure to trace ACT repressed Dio2 expression, declined T3 and then activated thyroid receptor-mediated signaling, thereby leading to integrated thyroid endocrine disruption in zebrafish larvae.

Marine mammals in the Barents Sea region have among the highest levels of contaminants recorded in the Arctic and the Atlantic walrus (Odobenus rosmarus rosmarus) is one of the most contaminated species within this region. We therefore investigated the relationships bewteen blubber concentrations of lipophilic persistent organic pollutants (POPs) and plasma concentrations of perfluoroalkyl substances (PFASs) and markers of endocrine and immune functions in adult male Atlantic walruses (n = 38) from Svalbard, Norway. To do so, we assessed plasma concentrations of five forms of thyroid hormones and transcript levels of genes related to the endocrine and immune systems as endpoints; transcript levels of seven genes in blubber and 23 genes in blood cells were studied. Results indicated that plasma total thyroxine (TT4) concentrations and ratio of TT4 and reverse triiodothyronine decreased with increasing blubber concentrations of lipophilic POPs. Blood cell transcript levels of genes involved in the function of T and B cells (FC like receptors 2 and 5, cytotoxic T-lymphocyte associated protein 4 and protein tyrosine phosphatase non-receptor type 22) were increased with plasma PFAS concentrations. These results suggest that changes in thyroid and immune systems in adult male walruses are linked to current levels of contaminant exposure.

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.

Perfluorododecanoic acid (PFDoA), a kind of perfluorinated carboxylic acid (PFCA) with 12 carbon atoms, has an extensive industrial utilization and is widespread in both wildlife and the water environment, and was reported to have the potential to cause a disruption in the thyroid hormone system homeostasis. In this study, zebrafish embryos/larvae were exposed to different concentrations of PFDoA (0, 0.24, 1.2, 6 mg/L) for 96 h post-fertilization (hpf). PFDoA exposure caused obvious growth restriction connected with the reduced thyroid hormones (THs) contents in zebrafish larvae, strengthening the interference effect on the growth of fish larvae. The transcriptional level of genes within the hypothalamic-pituitary-thyroid (HPT) axis was analyzed. The gene expression levels of thyrotropin-releasing hormone (trh) and corticotrophin-releasing hormone (crh) were upregulated upon exposure to 6 mg/L of PFDoA, and iodothyronine deiodinases (dio2) was upregulated in the 1.2 mg/L PFDoA group. The transcription of thyroglobulin (tg) and thyroid receptor (trβ) were significantly downregulated upon exposure to 1.2 mg/L and 6 mg/L of PFDoA. PFDoA could also decrease the levels of sodium/iodide symporter (nis) and transthyretin (ttr) gene expression in a concentration-dependent manner after exposure. A significant decrease in thyroid-stimulating hormoneβ (tshβ), uridinediphosphate-glucuronosyltransferase (ugt1ab) and thyroid receptor (trα) gene expression were observed at 6 mg/L PFDoA exposure. Upregulation and downregulation of iodothyronine deiodinases (dio1) gene expression were observed upon the treatment of 1.2 mg/L and 6 mg/L PFDoA, respectively. All the data demonstrated that gene expression in the HPT axis altered after different PFDoA treatment and the potential mechanisms of the disruption of thyroid status could occur at several steps in the process of synthesis, regulation, and action of thyroid hormones.