Ti3C2 (MXene) nanosheets disrupt spermatogenesis in male mice mediated by the ATM/p53 signaling pathway

作者全名："Wei, Yang; Bao, Ruilin; Hu, Le; Geng, Yanqing; Chen, Xuemei; Wen, Yixian; Wang, Yingxiong; Qin, Mao; Zhang, Yue; Liu, Xueqing"

作者地址："[Wei, Yang; Bao, Ruilin; Geng, Yanqing; Chen, Xuemei; Wen, Yixian; Wang, Yingxiong; Zhang, Yue; Liu, Xueqing] Chongqing Med Univ, Sch Publ Hlth, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China; [Hu, Le] Lanzhou Univ, Dept Obstet & Gynecol, Key Lab Gynecol Oncol Gansu Prov, Hosp 1, Lanzhou, Peoples R China; [Geng, Yanqing; Zhang, Yue] Chongqing Med Univ, Coll Basic Med, Chongqing, Peoples R China; [Qin, Mao] Chongqing Med Univ, Dept Androl Women & Childrens Hosp, Chongqing, Peoples R China; [Liu, Xueqing] Chongqing Med Univ, Dept Obstet & Gynecol, Women & Childrens Hosp, Chongqing, Peoples R China"

通信作者："Zhang, Y; Liu, XQ (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China.; Zhang, Y (通讯作者)，Chongqing Med Univ, Coll Basic Med, Chongqing, Peoples R China.; Liu, XQ (通讯作者)，Chongqing Med Univ, Dept Obstet & Gynecol, Women & Childrens Hosp, Chongqing, Peoples R China."

来源：BIOLOGY DIRECT

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001009487100002

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：18

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Spermatogenesis; Ti3C2 nanosheets; Spermatogonia; DNA damage; ATM; p53 signaling pathway

摘要："Background Two-dimensional ultrathin Ti3C2 nanosheets are increasingly being used in biomedical applications owing to their special physicochemical properties. But, the biological effects of its exposure on the reproductive system is still unclear. This study evaluated the reproductive toxicity of Ti3C2 nanosheets in the testes. Results Ti3C2 nanosheets at doses of 2.5 mg/kg bw and 5 mg/kg bw in mice caused defects in spermatogenic function, and we also clarified an underlying molecular mechanism of it in vivo and in vitro model. Ti3C2 nanosheets induced an increase of reactive oxygen species (ROS) in testicular and GC-1 cells, which in turn led to the imbalance in oxidative and antioxidant systems (also known as oxidative stress). Additionally, oxidative stress often induces cellular DNA strand damages via the oxidative DNA damages, which triggered cell cycle arrest in the G1/G0 phase, leading to cell proliferation inhibition and irreversible apoptosis. ATM/p53 signaling manifest key role in DNA damage repair (DDR), and we demonstrate that ATM/p53 signaling was activated, and mediated the toxic damage process caused by Ti3C2 nanosheet exposure. Conclusion Ti3C2 nanosheet-induced disruption of proliferation and apoptosis of spermatogonia perturbed normal spermatogenic function that was mediated by ATM/p53 signaling pathway. Our findings shed more light on the mechanisms of male reproductive toxicity induced by Ti3C2 nanosheets."

基金机构：Postdoctoral Program of Chongqing Natural Science Foundation [CSTB2022NSCQ-BHX0660]; Gansu Natural Science Foundation [21JR1RA108]

基金资助正文：This work was supported by the Postdoctoral Program of Chongqing Natural Science Foundation (No. CSTB2022NSCQ-BHX0660) and Gansu Natural Science Foundation under Grant No. 21JR1RA108.