Wnt10a downregulation contributes to MEHP-induced disruption of self-renewal and differentiation balance and proliferation inhibition in GC-1 cells: Insights from multiple transcriptomic profiling

作者全名："Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Wang, Siyuan; Zheng, Xiangqin; Zhao, Jie; Yu, Chengjun; Pei, Jun; Zhang, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui"

作者地址："[Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Wang, Siyuan; Zheng, Xiangqin; Zhao, Jie; Yu, Chengjun; Pei, Jun; Zhang, Jie; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wang, Siyuan; Zheng, Xiangqin; Zhao, Jie; Yu, Chengjun; Pei, Jun; Zhang, Jie; Long, Chunlan; Shen, Lianju] Chongqing Med Univ, Childrens Hosp, Pediat Res Inst, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Wang, Siyuan; Zheng, Xiangqin; Zhao, Jie; Yu, Chengjun; Pei, Jun; Zhang, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Chongqing Key Lab Children Urogenital Dev & Tissue, Childrens Hosp, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Wang, Siyuan; Zheng, Xiangqin; Zhao, Jie; Yu, Chengjun; Pei, Jun; Zhang, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Key Lab Child Dev & Disorders, Minist Educ, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Wang, Siyuan; Zheng, Xiangqin; Zhao, Jie; Yu, Chengjun; Pei, Jun; Zhang, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Wang, Siyuan; Zheng, Xiangqin; Zhao, Jie; Yu, Chengjun; Pei, Jun; Zhang, Jie; Long, Chunlan; Shen, Lianju; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China"

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

来源：ENVIRONMENTAL POLLUTION

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001037254600001

JCR分区：Q1

影响因子：7.6

年份：2023

卷号：333

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：MEHP; Germ cells; Wnt10a; Self-renew; Differentiation

摘要："Di (2-ethylhexyl) phthalate (DEHP), one of phthalic acid esters, has been widely used in daily products. Its main metabolite, mono (2-ethylhexyl) phthalate (MEHP) was reported to possess higher testicular toxicity than DEHP. To explore the precise mechanism in MEHP-induced testis damage, multiple transcriptomic sequencing was employed in spermatogonia cell line GC-1 cells treated with MEHP (0, 100, and 200 & mu;M) for 24 h. Integrative omics analysis and empirical validation revealed that Wnt signaling pathway was downregulated and wnt10a, one of hub genes, may be the key player in this process. Similar results were observed in DEHP-exposed rats. MEHP-induced disturbance of self-renewal and differentiation was dose-dependent. Moreover, self-renewal proteins were downregulated; the differentiation level was stimulated. Meanwhile, GC-1 proliferation was decreased. Stable transformation strain of wnt10a overexpression GC-1 cell line constructed from lentivirus was utilized in this study. The upregulation of Wnt10a significantly reversed the dysfunction of self-renewal and differentiation and promoted the cell proliferation. Finally, retinol, predicted to be useful in CONNECTIVITY MAP (cMAP), failed to rescue the damage caused by MEHP. Cumulatively, our findings revealed that the downregulation of Wnt10a induced the imbalance of self-renew and differentiation, and inhibition of cell proliferation in GC-1 cells after MEHP exposure."

基金机构："National Natural Science Foundation of China [81771566, 82071632]; Postgraduate Research Innovation Project of Chongqing Medical University [CYB22210]; Ministry of Education Key Laboratory of Child Development and Disorders [YBRP-202114]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (Grant number 81771566, 82071632) , the Postgraduate Research Innovation Project of Chongqing Medical University (Grant number CYB22210) , and the Youth Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders (Grant number YBRP-202114) ."