Polystyrene nanoplastics exposure triggers spermatogenic cell senescence via the Sirt1/ROS axis

作者全名：Liang, Yuehui; Yang, Yurui; Lu, Chunsheng; Cheng, Ya; Jiang, Xiao; Yang, Binwei; Li, Yawen; Chen, Qing; Ao, Lin; Cao, Jia; Han, Fei; Liu, Jinyi; Zhao, Lina

作者地址：[Liang, Yuehui; Zhao, Lina] Wuhan Univ, Sch Publ Hlth, Wuhan 430071, Peoples R China; [Yang, Yurui; Lu, Chunsheng; Cheng, Ya; Jiang, Xiao; Yang, Binwei; Li, Yawen; Chen, Qing; Ao, Lin; Cao, Jia; Han, Fei; Liu, Jinyi] Army Med Univ, Inst Toxicol, Coll Prevent Med, State Key Lab Trauma & Chem Poisoning,Minist Educ, Chongqing 400038, Peoples R China; [Yang, Yurui] China Med Univ, Sch Publ Hlth, Shenyang 110122, Peoples R China; [Han, Fei] Chongqing Med Univ, Sch Publ Hlth, Chongqing 400016, Peoples R China

通信作者：Zhao, LA (通讯作者)，Wuhan Univ, Sch Publ Hlth, Wuhan 430071, Peoples R China.; Han, F; Liu, JY (通讯作者)，Army Med Univ, Inst Toxicol, Coll Prevent Med, State Key Lab Trauma & Chem Poisoning,Minist Educ, Chongqing 400038, Peoples R China.; Han, F (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Chongqing 400016, Peoples R China.

来源：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001244098700001

JCR分区：Q1

影响因子：6.2

年份：2024

卷号：279

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Polystyrene nanoplastics; Reproductive toxicity; Senescence; Oxidative stress; Pterostilbene

摘要：Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs exposure on testicular cells and the underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with PS-NPs (80 nm) at different dosages (0, 10, and 40 mg/kg/day) for 60 days, and GC-1 cells were treated with PS-NPs in this study. Enlarged seminiferous tubule lumens and a loose and vacuolated layer of spermatogenic cells were observed in PS-NPs-exposed mice. Spermatogenic cells which may be one of the target cells for this reproductive damage, were decreased in the mice from PS-NPs group. PS-NPs caused spermatogenic cells to undergo senescence, manifested as elevated SA-beta-galactosidase activity and activated senescence-related signaling p53-p21/Rb-p16 pathways, and induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested the key role of reactive oxygen species (ROS) in PS-NPs-induced spermatogenic cell senescence, and this result was confirmed by measuring ROS levels. Moreover, ROS inhibition partially attenuated the senescence phenotype of spermatogenic cells and DNA damage. Using the male health atlas (MHA) database, Sirt1 was filtrated as the critical molecule in the regulation of testicular senescence. PS-NPs induced overexpression of the main ROS generator Nox2, downregulated Sirt1, increased p53 and acetylated p53 in vivo and in vitro, whereas these disturbances were partially restored by pterostilbene. In addition, pterostilbene intervention significantly alleviated the PS-NPs-induced spermatogenic cell senescence and attenuated ROS burst. Collectively, our study reveals that PS-NPs exposure can trigger spermatogenic cell senescence mediated by p53-p21/Rb-p16 signaling by regulating the Sirt1/ROS axis. Importantly, pterostilbene intervention may be a promising strategy to alleviate this damage.

基金机构：Key Program of National Natural Science Foundation of China [82130097]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0316, cstc2020jcyj- msxmX0419]

基金资助正文：This work was supported by the Key Program of National Natural Science Foundation of China (82130097) , and the Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0316, cstc2020jcyj- msxmX0419) .