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

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

机构地区：[1]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 [2]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

出　　处：《Journal of Pharmaceutical Analysis》2023年第8期880-893,共14页药物分析学报（英文版）

基　　金：supported by grants from the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600);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.:82201786,82141001,82274182,82074098,82173914);the CACMS Innovation Fund(Grant Nos.:CI2021A05101,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,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,ZZ15-ND-10).

摘　　要：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.

关 键 词：Single-cell sequence TRANSCRIPTOMICS TRIPTOLIDE Reproduction toxicity TESTIS 

分 类 号：R318.08[医药卫生—生物医学工程]