Single-cell transcriptomic dissection of the toxic impact of di(2-ethylhexyl) phthalate on immature testicular development at the neonatal stage

作者全名："Wei, Yuexin; Hong, Yifan; Yang, Liuqing; Wang, Junke; Zhao, Tianxin; Zheng, Xiangqin; Kang, Lian; Chen, Jiadong; Han, Lindong; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui"

作者地址："[Wei, Yuexin; Hong, Yifan; Wang, Junke; Zheng, Xiangqin; Kang, Lian; Chen, Jiadong; Han, Lindong; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China; [Hong, Yifan; Yang, Liuqing; Wang, Junke; Zheng, Xiangqin; Kang, Lian; Chen, Jiadong; Han, Lindong; Long, Chunlan; Shen, Lianju; Wu, Shengde] Chongqing Med Univ, Pediat Res Inst, Childrens Hosp, Chongqing 400014, Peoples R China; [Wei, Yuexin; Hong, Yifan; Yang, Liuqing; Wang, Junke; Zheng, Xiangqin; Kang, Lian; Chen, Jiadong; Han, Lindong; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing Key Lab Pediat,Childrens Hosp,Minist Edu, Chongqing 400014, Peoples R China; [Zhao, Tianxin] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangdong Prov Clin Res Ctr Child Hlth, Dept Urol, Guangzhou 510623, Peoples R China"

通信作者："Wu, SD (通讯作者)，Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China."

来源：FOOD AND CHEMICAL TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000985305600001

JCR分区：Q1

影响因子：3.9

年份：2023

卷号：176

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：DEHP; Single-cell transcriptome; Male germ cell; Spermatogenic niche

摘要："Di(2-ethylhexyl) phthalate (DEHP) early exposure leads to immature testicular injury, and we aimed to utilize single-cell RNA (scRNA) sequencing to comprehensively assess the toxic effect of DEHP on testicular develop-ment. Therefore, we gavaged pregnant C57BL/6 mice with 750 mg/kg body weight DEHP from gestational day 13.5 to delivery and performed scRNA sequencing of neonatal testes at postnatal day 5.5. The results revealed the gene expression dynamics in testicular cells. DEHP disrupted the developmental trajectory of germ cells and the balance between the self-renewal and differentiation of spermatogonial stem cells. Additionally, DEHP caused an abnormal developmental trajectory, cytoskeletal damage and cell cycle arrest in Sertoli cells; disrupted the metabolism of testosterone in Leydig cells; and disturbed the developmental trajectory in peritubular myoid cells. Elevated oxidative stress and excessive apoptosis mediated by p53 were observed in almost all testicular cells. The intercellular interactions among four cell types were altered, and biological processes related to glial cell line-derived neurotrophic factor (GDNF), transforming growth factor-beta (TGF-beta), NOTCH, platelet-derived growth factor (PDGF) and WNT signaling pathways were enriched after DEHP treatment. These findings systematically describe the damaging effects of DEHP on the immature testes and provide substantial novel insights into the reproductive toxicity of DEHP."

基金机构："National Natural Sci- ence Foundation of China [82071632]; Postgraduate Research Innovation Project of Chongqing Medical University [CYB22210]; Guangdong Basic and Applied Basic Research Foundation [2022A1515012576, 2020A1515110796]; Research Foundation of Guangzhou Women and Children's Medical Center for Clinical Doctor"

基金资助正文："This study was supported by grants from the National Natural Sci- ence Foundation of China (Grant No. 82071632) , the Postgraduate Research Innovation Project of Chongqing Medical University (Grant number CYB22210) , the Guangdong Basic and Applied Basic Research Foundation (Grant number 2022A1515012576, 2020A1515110796) , and the Research Foundation of Guangzhou Women and Children's Medical Center for Clinical Doctor. We thank American Journal Experts ( www.aje.com ) for its linguistic assistance during the preparation of this manuscript. We thank Professor Yupeng Cun for his kind help with the single-cell data analysis and guidance during this project. The authors sincerely acknowledge the anonymous reviewers for their insights and comments, which further improved the quality of the manuscript."