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Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes

Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were a...

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Autores principales: Zheng, Xiangqin, Wei, Yuexin, Chen, Jiadong, Wang, Xia, Li, Dinggang, Yu, Chengjun, Hong, Yifan, Shen, Lianju, Long, Chunlan, Wei, Guanghui, Wu, Shengde
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142862/
https://www.ncbi.nlm.nih.gov/pubmed/37112555
http://dx.doi.org/10.3390/toxics11040328
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author Zheng, Xiangqin
Wei, Yuexin
Chen, Jiadong
Wang, Xia
Li, Dinggang
Yu, Chengjun
Hong, Yifan
Shen, Lianju
Long, Chunlan
Wei, Guanghui
Wu, Shengde
author_facet Zheng, Xiangqin
Wei, Yuexin
Chen, Jiadong
Wang, Xia
Li, Dinggang
Yu, Chengjun
Hong, Yifan
Shen, Lianju
Long, Chunlan
Wei, Guanghui
Wu, Shengde
author_sort Zheng, Xiangqin
collection PubMed
description Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.
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spelling pubmed-101428622023-04-29 Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes Zheng, Xiangqin Wei, Yuexin Chen, Jiadong Wang, Xia Li, Dinggang Yu, Chengjun Hong, Yifan Shen, Lianju Long, Chunlan Wei, Guanghui Wu, Shengde Toxics Article Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes. MDPI 2023-03-30 /pmc/articles/PMC10142862/ /pubmed/37112555 http://dx.doi.org/10.3390/toxics11040328 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zheng, Xiangqin
Wei, Yuexin
Chen, Jiadong
Wang, Xia
Li, Dinggang
Yu, Chengjun
Hong, Yifan
Shen, Lianju
Long, Chunlan
Wei, Guanghui
Wu, Shengde
Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes
title Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes
title_full Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes
title_fullStr Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes
title_full_unstemmed Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes
title_short Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes
title_sort difenoconazole exposure induces retinoic acid signaling dysregulation and testicular injury in mice testes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142862/
https://www.ncbi.nlm.nih.gov/pubmed/37112555
http://dx.doi.org/10.3390/toxics11040328
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