A single-cell landscape of triptolide-associated testicular toxicity in mice

Wei Zhang; Siyu Xia; Jinhuan Ou; Min Cao; Guangqing Cheng; Zhijie Li; Jigang Wang; Chuanbin Yang

doi:10.1016/j.jpha.2023.04.006

Volume 13 Issue 8

Aug. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(8): 880-893

Wei Zhang, Siyu Xia, Jinhuan Ou, Min Cao, Guangqing Cheng, Zhijie Li, Jigang Wang, Chuanbin Yang. A single-cell landscape of triptolide-associated testicular toxicity in mice[J]. Journal of Pharmaceutical Analysis, 2023, 13(8): 880-893. doi: 10.1016/j.jpha.2023.04.006

Citation:

Wei Zhang, Siyu Xia, Jinhuan Ou, Min Cao, Guangqing Cheng, Zhijie Li, Jigang Wang, Chuanbin Yang. A single-cell landscape of triptolide-associated testicular toxicity in mice[J]. Journal of Pharmaceutical Analysis, 2023, 13(8): 880-893. doi: 10.1016/j.jpha.2023.04.006

Citation:

Wei Zhang, Siyu Xia, Jinhuan Ou, Min Cao, Guangqing Cheng, Zhijie Li, Jigang Wang, Chuanbin Yang. A single-cell landscape of triptolide-associated testicular toxicity in mice[J]. Journal of Pharmaceutical Analysis, 2023, 13(8): 880-893. doi: 10.1016/j.jpha.2023.04.006

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A single-cell landscape of triptolide-associated testicular toxicity in mice

doi: 10.1016/j.jpha.2023.04.006

a. Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, China;
b. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 10700, China

Funds:

The work was supported by grants from the National Key Research and Development Program of China (Grant Nos.: 2020YFA0908000 and 2022YFC2303600), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Grant No.: ZYYCXTD-C-202002), the National Natural Science Foundation of China (Grant Nos.: 82201786, 82141001, 82274182, 82074098 and 82173914), the CACMS Innovation Fund (Grant Nos.: CI2021A05101 and CI2021A05104), the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (Grant No.: CI2021B014), the Science and Technology Foundation of Shenzhen (Grant Nos.: JCYJ20220818102613029, JCYJ20210324114014039, and JCYJ20210324115800001), Guangdong Basic and Applied Basic Research Foundation (Grant Nos.: 2020A1515110549, 2021A1515110646), the Science and Technology Foundation of Shenzhen (Shenzhen Clinical Medical Research Center for Geriatric Diseases), the National Key R&D Program of China Key projects for international cooperation on science, technology and innovation (Grant No.: 2020YFE0205100), and the Fundamental Research Funds for the Central Public Welfare Research Institutes (Grant Nos.: ZZ14-YQ-050, ZZ14-YQ-051, ZZ14-YQ-052, ZZ14-FL-002, ZZ14-ND-010 and ZZ15-ND-10).

Received Date: Dec. 28, 2022
Rev Recd Date: Apr. 09, 2023
Available Online: Aug. 29, 2023

Abstract

Abstract

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook. F. Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases, its well-known safety issues, especially reproductive toxicity has aroused concerns. However, a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking. Here, we observed testicular toxicity after 14 days of triptolide exposure, and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment. We identified triptolide-associated shared and cell-type specific differentially expressed genes, enriched pathways, and ligand-receptor pairs in different cell types of mouse testes. In addition to the loss of germ cells, our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes, suggesting a critical role of inflammation in triptolide-induced testicular injury. We also found increased reactive oxygen species (ROS) signaling and downregulated pathways associated with spermatid development in somatic cells, especially Leydig and Sertoli cells, in triptolide-treated mice, indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity. Overall, our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution, providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.
- Single-cell sequence,
- Transcriptomics,
- Triptolide,
- Reproduction toxicity,
- Testis

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