Methimazole disrupted skeletal ossification and muscle fiber transition in Bufo gargarizans larvae

Methimazole (MMI) is an emerging endocrine disrupting chemical (EDC) due to its increasing use in the treatment of thyrotoxicosis (hyperthyroidism), but its potential impact on amphibian development remains largely unexplored. In the present study, the effects of 8 mg/L MMI and 1 μg/L thyroxine (T4)...

Full description

Saved in:
Bibliographic Details
Main Authors: Fei Wei, Xueyi Wu, Hongyuan Wang, Yongpu Zhang, Lei Xie
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S014765132500020X
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832591000790368256
author Fei Wei
Xueyi Wu
Hongyuan Wang
Yongpu Zhang
Lei Xie
author_facet Fei Wei
Xueyi Wu
Hongyuan Wang
Yongpu Zhang
Lei Xie
author_sort Fei Wei
collection DOAJ
description Methimazole (MMI) is an emerging endocrine disrupting chemical (EDC) due to its increasing use in the treatment of thyrotoxicosis (hyperthyroidism), but its potential impact on amphibian development remains largely unexplored. In the present study, the effects of 8 mg/L MMI and 1 μg/L thyroxine (T4) exposure on skeletal ossification and muscle development in Bufo gargarizans tadpoles were comprehensively investigated by double skeletal staining, histological analysis and RNA sequencing. Our results indicated that MMI treatment down-regulated the expression levels of ossification-related genes (e.g., BMPs, MMPs, and Wnt9a) in cartilage, thereby delaying chondrocyte apoptosis and inhibiting hindlimb ossification. Muscle sarcomere was elongated in both the MMI and T4 treatment groups, which may lead to muscle weakness and consequently affect land motion. Additionally, we evaluated the expression levels of fast muscle-related genes (TNNI2 and TNNT3) and slow muscle-related genes (TNNI1 and TNNT1), revealing an opposite trend in the transition from fast to slow muscle after T4 and MMI exposures. In conclusion, these findings fill the data gap regarding MMI contamination in aquatic environments by revealing the negative effects of MMI on amphibian bone and muscle development. Future studies should address the toxicity of EDCs to wildlife and inform aquatic ecosystem conservation strategies.
format Article
id doaj-art-f2fa8aaade0945c5bd7f2f7a69bdf39b
institution Kabale University
issn 0147-6513
language English
publishDate 2025-01-01
publisher Elsevier
record_format Article
series Ecotoxicology and Environmental Safety
spelling doaj-art-f2fa8aaade0945c5bd7f2f7a69bdf39b2025-01-23T05:26:06ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117684Methimazole disrupted skeletal ossification and muscle fiber transition in Bufo gargarizans larvaeFei Wei0Xueyi Wu1Hongyuan Wang2Yongpu Zhang3Lei Xie4Life and Environmental Science College, Wenzhou University, Wenzhou 325003, China; College of Life Science, Shaanxi Normal University, Xi’an 710119, ChinaLife and Environmental Science College, Wenzhou University, Wenzhou 325003, ChinaCollege of Life Science, Shaanxi Normal University, Xi’an 710119, ChinaLife and Environmental Science College, Wenzhou University, Wenzhou 325003, China; Zhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, Wenzhou University, Wenzhou 325003, China; Corresponding authors at: Life and Environmental Science College, Wenzhou University, Wenzhou 325003, China.Life and Environmental Science College, Wenzhou University, Wenzhou 325003, China; Zhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, Wenzhou University, Wenzhou 325003, China; Corresponding authors at: Life and Environmental Science College, Wenzhou University, Wenzhou 325003, China.Methimazole (MMI) is an emerging endocrine disrupting chemical (EDC) due to its increasing use in the treatment of thyrotoxicosis (hyperthyroidism), but its potential impact on amphibian development remains largely unexplored. In the present study, the effects of 8 mg/L MMI and 1 μg/L thyroxine (T4) exposure on skeletal ossification and muscle development in Bufo gargarizans tadpoles were comprehensively investigated by double skeletal staining, histological analysis and RNA sequencing. Our results indicated that MMI treatment down-regulated the expression levels of ossification-related genes (e.g., BMPs, MMPs, and Wnt9a) in cartilage, thereby delaying chondrocyte apoptosis and inhibiting hindlimb ossification. Muscle sarcomere was elongated in both the MMI and T4 treatment groups, which may lead to muscle weakness and consequently affect land motion. Additionally, we evaluated the expression levels of fast muscle-related genes (TNNI2 and TNNT3) and slow muscle-related genes (TNNI1 and TNNT1), revealing an opposite trend in the transition from fast to slow muscle after T4 and MMI exposures. In conclusion, these findings fill the data gap regarding MMI contamination in aquatic environments by revealing the negative effects of MMI on amphibian bone and muscle development. Future studies should address the toxicity of EDCs to wildlife and inform aquatic ecosystem conservation strategies.http://www.sciencedirect.com/science/article/pii/S014765132500020XAmphibianMethimazoleThyroxineEndochondral ossificationMuscle transformation
spellingShingle Fei Wei
Xueyi Wu
Hongyuan Wang
Yongpu Zhang
Lei Xie
Methimazole disrupted skeletal ossification and muscle fiber transition in Bufo gargarizans larvae
Ecotoxicology and Environmental Safety
Amphibian
Methimazole
Thyroxine
Endochondral ossification
Muscle transformation
title Methimazole disrupted skeletal ossification and muscle fiber transition in Bufo gargarizans larvae
title_full Methimazole disrupted skeletal ossification and muscle fiber transition in Bufo gargarizans larvae
title_fullStr Methimazole disrupted skeletal ossification and muscle fiber transition in Bufo gargarizans larvae
title_full_unstemmed Methimazole disrupted skeletal ossification and muscle fiber transition in Bufo gargarizans larvae
title_short Methimazole disrupted skeletal ossification and muscle fiber transition in Bufo gargarizans larvae
title_sort methimazole disrupted skeletal ossification and muscle fiber transition in bufo gargarizans larvae
topic Amphibian
Methimazole
Thyroxine
Endochondral ossification
Muscle transformation
url http://www.sciencedirect.com/science/article/pii/S014765132500020X
work_keys_str_mv AT feiwei methimazoledisruptedskeletalossificationandmusclefibertransitioninbufogargarizanslarvae
AT xueyiwu methimazoledisruptedskeletalossificationandmusclefibertransitioninbufogargarizanslarvae
AT hongyuanwang methimazoledisruptedskeletalossificationandmusclefibertransitioninbufogargarizanslarvae
AT yongpuzhang methimazoledisruptedskeletalossificationandmusclefibertransitioninbufogargarizanslarvae
AT leixie methimazoledisruptedskeletalossificationandmusclefibertransitioninbufogargarizanslarvae