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

Zhang, Wei1; Xia, Siyu1; Ou, Jinhuan1; Cao, Min1; Cheng, Guangqing2; Li, Zhijie1; Wang, Jigang1,2; Yang, Chuanbin1

2023-08-01

10.1016/j.jpha.2023.04.006

JOURNAL OF PHARMACEUTICAL ANALYSIS   Impact Factor & Quartile

2095-1779

2214-0883

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 triptolideinduced testicular injury. We also found increased reactive oxygen species (ROS) signaling and down regulated 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.& COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Single-cell sequence Transcriptomics Triptolide Reproduction toxicity Testis

SCI

English

First ; Corresponding

Innovation Team and Talents Cultivation Program of National Administration of Tradi-tional Chinese Medicine["2020YFA0908000","2022YFC2303600"] ; Na-tional Natural Science Foundation of China[ZYYCXTD-C-2020 02] ; CACMS Innova-tion Fund["82201786","82141001","82274182","82074098","82173914"] ; Sci-entific and Technological Innovation Project of China Academy of Chinese Medical Sciences["CI2021A05101","CI2021A05104"] ; Science and Technology Foundation of Shenzhen[CI2021B014] ; Guangdong Basic and Applied Basic Research Foundation["JCYJ20220818102613029","JCYJ20210324114014039","JCYJ20210324115800001"] ; Science and Technology Foundation of Shenzhen (Shenzhen Clinical Medical Research Center for Geriatric Diseases)["2020A1515110549","2021A1515110646"] ; National Key Ramp;D Program of China Key projects for international cooperation on science, technology and innovation[2020YFE0205100] ; null[ZZ14-YQ-050] ; null[ZZ14-YQ-051] ; null[ZZ14-YQ-052] ; null[ZZ14-FL-0 02] ; null[ZZ14-ND-010] ; null[ZZ15-ND-10]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:001071573200001

ELSEVIER

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp,Shenzhen Clin Res Ctr Geriat, Affiliated Hosp 1,Dept Nephrol,Shenzhen Key Lab Ki, Shenzhen 518020, Guangdong, Peoples R China
2.China Acad Chinese Med Sci, Inst Chinese Mat Med, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, 10700, Beijing, Peoples R China

Zhang, Wei,Xia, Siyu,Ou, Jinhuan,et al. A single-cell landscape of triptolide-associated testicular toxicity in mice[J]. JOURNAL OF PHARMACEUTICAL ANALYSIS,2023,13(8).

Zhang, Wei.,Xia, Siyu.,Ou, Jinhuan.,Cao, Min.,Cheng, Guangqing.,...&Yang, Chuanbin.(2023).A single-cell landscape of triptolide-associated testicular toxicity in mice.JOURNAL OF PHARMACEUTICAL ANALYSIS,13(8).

Zhang, Wei,et al."A single-cell landscape of triptolide-associated testicular toxicity in mice".JOURNAL OF PHARMACEUTICAL ANALYSIS 13.8(2023).