实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (6): 626-635.DOI: 10.12300/j.issn.1674-5817.2024.068

• 人类疾病动物模型 • 上一篇    下一篇

大气细颗粒物PM2.5暴露动物模型建立方法及在生殖毒性研究中的应用进展

田芳1,2()(), 潘滨1,2(), 史佳怡1, 徐燕意2()(), 李卫华1()()   

  1. 1.上海市生物医药技术研究院, 国家卫生健康委员会生育调节药械重点实验室, 上海生殖健康药具工程技术研究中心, 上海 200237
    2.复旦大学公共卫生学院, 上海 200032
  • 收稿日期:2024-05-11 修回日期:2024-08-01 出版日期:2025-01-04 发布日期:2024-12-25
  • 通讯作者: 李卫华(1973—),女,博士,研究员,博士生导师,研究方向:化学物的生殖发育毒性研究和新型生育调节药物的研发。E-mail: iamliwehua@foxmail.com。ORCID:0000-0003-4596-9088;
    徐燕意(1988—),女,博士,副教授,研究方向:大气污染物的毒性机制及跨代效应。E-mail: yanyi_xu@fudan.edu.cn。ORCID:0000-0003-0270-2017
  • 作者简介:田芳(1985—),女,高级实验师,博士研究生在读,研究方向:化学物的生殖发育毒性研究及新型生育调节药物的研发。E-mail: 376616808@qq.com
    潘滨(1992—),男,博士研究生在读,研究方向:生殖相关药物的临床前药理与毒理学研究。E-mail: 18211020079@fudan.edu.cn
  • 基金资助:
    国家自然科学基金资助项目“线粒体蛋白硫巯基化修饰对精子运动的调控机制”(32270910);上海市科技计划项目“乙酸避孕凝胶的Ⅰ期临床研究”(22S11904900)

Advances in Development of PM2.5-Exposed Animal Models and Their Application in Reproductive Toxicity Research

TIAN Fang1,2()(), PAN Bin1,2(), SHI Jiayi1, XU Yanyi2()(), LI Weihua1()()   

  1. 1.National Health Commission Key Lab of Reproduction Regulation, Shanghai Engineering Research Center of Reproductive Health Drug and Devices, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, China
    2.School of Public Health, Fudan University, Shanghai 200032, China
  • Received:2024-05-11 Revised:2024-08-01 Published:2024-12-25 Online:2025-01-04
  • Contact: LI Weihua (ORCID: https://orcid.org/0000-0003-4596-9088), E-mail: iamliwehua@foxmail.com;
    XU Yanyi (ORCID: https://orcid.org/0000-0003-0270-2017), E-mail: yanyi_xu@fudan.edu.cn

摘要:

大气细颗粒物(particulate matter 2.5,PM2.5)是雾霾的主要成分,对人类生殖健康的潜在影响已成为公共卫生领域的关注焦点。建立合适的动物模型对于深入开展PM2.5暴露所引起的生殖毒性及其机制研究尤为关键。本综述基于近年来发表的相关文献,总结了当前PM2.5生殖毒性研究的动物模型建立方法和应用评价指标。PM2.5暴露的建模方法主要有全身吸入暴露和气管内滴注暴露。其中,全身吸入暴露虽然能较好地模拟人体实际吸入环境,但对实验设备要求高;而气管内滴注方法虽然成本较低、操作简单,却难以精确模拟PM2.5在自然吸入过程中的分布和沉积。因此,研究者在选择暴露方式时需综合权衡,以提高造模的严谨性并尽可能真实地模拟人类暴露条件。本综述进一步总结PM2.5暴露生殖毒性的应用评价指标,发现雄性生殖毒性的评价指标主要有精子质量降低、睾丸组织结构损伤和激素水平失衡;雌性生殖毒性的评价指标主要有卵巢储备功能降低、内分泌功能失衡、子宫内膜受损和围产期不良反应等。此外,本综述提出:需要关注PM2.5的化合物成分分析,探索含有不同化学成分如重金属和多环芳烃等颗粒物对生殖系统的作用靶点及机制;还需要开展长期研究,评估PM2.5暴露对动物及其后代生殖健康的影响,以预测人类可能面临的长期风险;另外还应进行跨学科合作,鼓励环境科学、毒理学、生殖医学等多学科间协作,以综合评估PM2.5的环境健康风险并为制定综合性的防治策略提供科学依据。本综述通过总结PM2.5导致生殖功能异常的动物建模方法及其应用评价,可为PM2.5的生殖毒性研究提供方法学参考。

关键词: 大气细颗粒物, PM2.5, 生殖毒性, 动物模型

Abstract:

Atmospheric fine particulate matter (particulate matter 2.5,PM2.5) is a major component of haze, and its potential hazards to human reproductive health have garnered widespread attention. Establishing appropriate animal models is crucial for in-depth research into the reproductive toxicity of PM2.5 exposure and its underlying mechanisms. This paper, based on recent literature, summarizes current methods for establishing PM2.5-exposed animal models and the evaluation criteria for reproductive toxicity research. The primary modeling methods for PM2.5 exposure include whole-body inhalation exposure and intratracheal instillation exposure. While whole-body inhalation exposure effectively simulates real-life human inhalation environments, it requires sophisticated experimental equipment. Conversely, intratracheal instillation exposure is more cost-effective and easier to operate but faces challenges in accurately mimicking the distribution and deposition of PM2.5 during natural inhalation. Therefore, researchers must carefully weigh these exposure methods to enhance model rigor and achieve the most realistic simulation of human exposure conditions. When summarizing the application evaluation indicators of PM2.5-induced reproductive toxicity, this review finds that the main indicators of male reproductive toxicity include reduced sperm quality, testicular tissue damage, and hormonal imbalances. For female reproductive toxicity, the primary indicators are reduced ovarian reserve, endocrine dysfunction, endometrial damage, and adverse perinatal reactions. Additionally, this review highlights the need for detailed chemical composition analysis of PM2.5, exploring the reproductive toxic targets and mechanisms of particles containing different chemical components, such as heavy metals and polycyclic aromatic hydrocarbons. Long-term studies are also necessary to assess the effects of PM2.5 exposure on reproductive health and transgenerational effects, to predict potential long-term risks for humans. Additionally, interdisciplinary collaboration should be encouraged, involving cooperation between environmental science, toxicology, reproductive medicine, and other disciplines, to comprehensively assess the environmental health risks of PM2.5 and provide scientific support for the development of integrated prevention and control strategies. This review summarizes animal modeling methods, evaluation criteria, and their applications, providing valuable methodological references for future reproductive toxicity research on PM2.5.

Key words: Atmospheric fine particulate matter, PM2.5, Reproductive toxicity, Animal model

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