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揭示环境暴露与睾丸损伤之间的联系:自噬和氧化应激失衡的启示

Unveiling the nexus between environmental exposures and testicular damages: revelations from autophagy and oxidative stress imbalance.

作者信息

Kong Xiuwen, Wang Xinda, Xia Qiushi, Hu Qingqing, Yu Wenqian, Huang Qiuru, Li Jiaxin, Wang Chenyu, Lin Ziwen, Liu Yiheng, Qi Yujuan, Tan Xiaofang, Zheng Bo, Yu Jun

机构信息

Institute of Reproductive Medicine, Jiangsu Province Key Laboratory in University for Inflammation and Molecular Drug Target, Medical School of Nantong University, Nantong University, Nantong, 226001, China.

Reproductive medicine Center, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, 226001, China.

出版信息

Cell Death Discov. 2025 May 29;11(1):258. doi: 10.1038/s41420-025-02543-4.

Abstract

Recent evidence consolidates the deleterious impact of environmental exposure on testicular damage. Environmental exposures can instigate testicular toxicity, causing damage to the Sertoli-Sertoli cell-mediated blood-testis barrier (BTB) integrity, alterations in hormone levels orchestrated by aberrant Leydig cells, and disruption of spermatogenesis. Despite diverse study designs and methodologies, a consensus is emerging on how environmental factors induce oxidative stress by elevating ROS levels, affecting autophagy through pathways such as the ROS-mediated mTOR signaling pathway, ultimately culminating in testicular damage. This review synthesizes existing literature on how environmental exposures, including metals, air pollutants, industrial contaminants, and pesticides, disturb testicular homeostasis via autophagy-mediated oxidative stress, highlighting recent significant advancements. It also explores interventions like antioxidant support and autophagy regulation to alleviate testicular damage. These findings underscore the importance of elucidating the mechanisms of autophagy influenced by environmental exposures in disrupting the equilibrium of oxidative stress, identifying potential drug targets, and establishing a groundwork for enhancing future treatments and clinical management of testicular injuries.

摘要

最近的证据证实了环境暴露对睾丸损伤的有害影响。环境暴露可引发睾丸毒性,导致支持细胞-支持细胞介导的血睾屏障(BTB)完整性受损、异常睾丸间质细胞协调的激素水平改变以及精子发生中断。尽管研究设计和方法各不相同,但关于环境因素如何通过升高活性氧(ROS)水平诱导氧化应激、通过ROS介导的哺乳动物雷帕霉素靶蛋白(mTOR)信号通路等途径影响自噬,最终导致睾丸损伤,正在形成共识。本综述综合了现有文献,阐述了包括金属、空气污染物、工业污染物和农药在内的环境暴露如何通过自噬介导的氧化应激扰乱睾丸内环境稳定,突出了近期的重大进展。它还探讨了抗氧化支持和自噬调节等干预措施以减轻睾丸损伤。这些发现强调了阐明环境暴露影响自噬的机制在破坏氧化应激平衡、确定潜在药物靶点以及为加强未来睾丸损伤治疗和临床管理奠定基础方面的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87c2/12122914/5de3f22c9a11/41420_2025_2543_Fig1_HTML.jpg

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