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Methimazole and sodium perchlorate exert anti-thyroidal effects in the T3-induced Xenopus laevis metamorphosis assay: A rapid assay for screening thyroid disrupting chemicals.
Zhou W
,
Qin ZF
,
Li YY
,
Li JB
,
Shi YL
,
Dong MX
,
Li X
,
Zhang YJ
,
He YD
.
???displayArticle.abstract??? Thyroid disrupting chemicals (TDCs) have received much attention due to their potential adverse effects on animal and human health, which calls for rapid screen assays to identify them. The triiodothyronine (T3)-induced Xenopus metamorphosis assay (TiXMA) we developed previously has been successfully applied to the detection of the TDCs disrupting thyroid hormone (TH) signaling. Here, we attempted to expand the application of the TiXMA to the screening of the TDCs interfering with the hypothalamic-pituitary-thyroid (HPT) axis. Two well-known TH synthesis inhibitors methimazole (MMI) and sodium perchlorate (SP) were employed to test the sensitivity of the TiXMA to the TDCs interfering with the HPT axis. As expected, we observed that the two chemicals concentration-dependently antagonized T3-induced morphological changes and body weight reduction of X. laevis tadpoles following 96 h-exposure, in parallel with blocked thyroid development and down-regulated tshβ expression in the brain. All the data show that both MMI and SP exert inhibitory effects on T3-induced metamorphosis, indicating that the TiXMA is capable of screening the TDCs interfering with the HPT axis. In comparison with Amphibian Metamorphosis Assay (AMA), a 21-day assay for screening the TDCs interfering with the HPT axis, the TiXMA has a remarkable advantage of shorter exposure duration (96 h).
Fig. 1. Relative body weight of Xenopus laevis after 96-h exposure to methimazole (MMI), sodium perchlorate (SP), or co-exposure to each chemical and T3. Data are shown as mean±SD. The data came from three replicate tanks with six tadpoles per tank for each treatment (n=3). Different lowercases indicate significant difference among T3 treatment and T3 + MMI (SP) of different concentrations.
Fig. 2. Gross morphology (A) and quantitative parameters (B) of Xenopus laevis after 96-h exposure to methimazole (MMI) in the absence or presence of T3. HA, head area; MW, mouth width; ULBW/BL, unilateral brain width/brain length; HLL/SVL, hindlimb length/snout-vent length. Data are shown as mean±SD. The data came from three replicate tanks with six tadpoles per tank for each treatment (n=3). Different lowercases indicate significant difference among T3 treatment and T3 + MMI of different concentrations .
Fig. 3. Gross morphology (A) and quantitative parameters (B) of Xenopus laevis after 96-h exposure to sodium perchlorate (SP) in the absence or presence of T3. HA, head area; MW, mouth width; ULBW/BL, unilateral brain width/brain length; HLL/SVL, hindlimb length/snout-vent length. Data are shown as mean±SD. The data came from three replicate tanks with six tadpoles per tank for each treatment (n=3). Different lowercases indicate significant difference among T3 treatment and T3 + SP of different concentrations .
Fig. 4. Relative expression of thyroid hormone (TH)-response genes in intestines of Xenopus laevis after 24-h exposure to (A) methimazole (MMI) and (B) sodium perchlorate (SP) in the absence or presence of T3. Data are shown as mean±SEM. The data came from three replicate tanks with three tadpoles per tank for each treatment (n=3). Different lowercases indicate significant difference among T3 treatment and T3 + MMI (SP) of different concentrations.
Fig. 5. Thyroid gland histology (A), colloid area (B) and tshβ expression (C) of Xenopus laevis after 96-h exposure to methimazole (MMI) in the absence or presence of T3. Quantitative data of tshβ gene expression are shown as mean ± SEM, and other data are shown as mean ± SD. The data came from three tadpoles for each treatment (n=3). Different lowercases indicate significant difference among T3 treatment and T3 + MMI of different concentrations.
Fig. 6. Thyroid gland histology (A), colloid area (B) and tshβ expression (C) of Xenopus laevis after 96-h exposure to sodium perchlorate (SP) in the absence or presence of 1 nM T3. Quantitative data of tshβ gene expression are shown as mean ± SEM, and other data are shown as mean ± SD. The data came from three tadpoles for each treatment (n=3). Different lowercases indicate significant difference among T3 treatment and T3 + SP of different concentrations.
