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
田芳1,2()(
), 潘滨1,2(
), 史佳怡1, 徐燕意2(
)(
), 李卫华1(
)(
)
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;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;基金资助:
TIAN Fang1,2()(
), PAN Bin1,2(
), SHI Jiayi1, XU Yanyi2(
)(
), LI Weihua1(
)(
)
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;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。
中图分类号:
田芳,潘滨,史佳怡,等. 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[J]. 实验动物与比较医学, 2024, 44(6): 626-635. DOI: 10.12300/j.issn.1674-5817.2024.068.
TIAN Fang,PAN Bin,SHI Jiayi,et al. Advances in Development of PM2.5-Exposed Animal Models and Their Application in Reproductive Toxicity Research[J]. Laboratory Animal and Comparative Medicine, 2024, 44(6): 626-635. DOI: 10.12300/j.issn.1674-5817.2024.068.
动物 Animal | PM2.5暴露浓度 Exposure concentration of PM2.5 | PM2.5暴露时间 Exposure duration of PM2.5 | 生殖毒性相关表型 Associated phenotypes of reproductive toxicity |
---|---|---|---|
C57BL/6小鼠,雄性,8周龄 C57BL/6 mouse, male, 8 weeks old | FA:60 µg/m3; CAP:488 µg/m3 | 6 h/d,共8周 | 精母细胞存在明显的病理损伤[ |
C57BL/6小鼠,雄性,6~8周龄 C57BL/6 mouse, male, 6-8 weeks old | FA:0.39 µg/m3; UA:59.75 µg/m3; CAP:483.61 µg/m3 | 6 h/d,5 d/周,共5周 | 精子活力降低[ |
C57BL/6小鼠,雄性,6周龄 C57BL/6 mouse, male, 6 weeks old | UA:94.84 µg/m3; CAP:900.21 µg/m3 | 6 h/d,分别暴露8周和16周 | 精子数量减少,活力降低,睾丸支持细胞空泡化,生精细胞变性[ |
C57BL/6小鼠,雄性,8周龄 C57BL/6 mouse, male, 8 weeks old | FA:0 µg/m3; CAP:75.78 µg/m3 | 60 d | 子代出生数量减少,睾丸重量减轻,精子数量减少,睾酮水平下降[ |
C57BL/6小鼠,雄性,8周龄 C57BL/6 mouse, male, 8 weeks old | FA:4.5 µg/m3; CAP:72.26 µg/m3 | 8 h/d,5 d/周,连续暴露16周 | 精子数量减少,精子活力下降,睾酮水平下降[ |
SD大鼠,雄性,6周龄 SD rat, male, 6 weeks old | FA:0.70 µg/m3; CAP:16.7 µg/m3 | 暴露8个月 | 睾丸内脂质紊乱[ |
Wistar大鼠,雄性,6周龄 Wistar rat, male, 6 weeks old | 对照组:0.02~0.18 mg/m3; 4倍浓缩组:0.06~0.81 mg/m3; 8倍浓缩组:0.11~1.60 mg/m3 | 8 h/d,连续3个月 | 间质水肿,生精精管细胞层次减少,各级生精细胞排列紊乱甚至缺失[ |
C57BL/6小鼠,雌性,8周龄 C57BL/6 mouse, female, 8 weeks old | FA:2.4 µg/m3; CAP:49.4 µg/m3 | 孕前每天暴露12 h,7 d/周,暴露4周,孕期继续暴露直到子代出生 | 母代卵巢储备降低,子代小鼠在出生后第3天和出生后第7天的原始卵泡和总卵泡数量均减少[ |
C57BL/6小鼠,雌性,4月龄 C57BL/6 mouse, female, 4 months old | FA:<5 µg/m3; CAP:110~130 µg/m3 | 5 h/d,4 h/周,持续12周 | 生长卵泡凋亡,卵巢储备降低[ |
C57BL/6小鼠,雌性,4周龄 C57BL/6 mouse, female, 4 weeks old | FA:3.93 µg/m3; CAP:128.1 µg/m3 | 8 h/d,5 d/周,共9周 | 卵巢闭锁[ |
表1 用于生殖毒性研究的PM2.5吸入暴露模型的造模方法和相关表型
Table 1 Modeling methods and associated phenotypes of PM2.5 inhalation exposure models for reproductive toxicity studies
动物 Animal | PM2.5暴露浓度 Exposure concentration of PM2.5 | PM2.5暴露时间 Exposure duration of PM2.5 | 生殖毒性相关表型 Associated phenotypes of reproductive toxicity |
---|---|---|---|
C57BL/6小鼠,雄性,8周龄 C57BL/6 mouse, male, 8 weeks old | FA:60 µg/m3; CAP:488 µg/m3 | 6 h/d,共8周 | 精母细胞存在明显的病理损伤[ |
C57BL/6小鼠,雄性,6~8周龄 C57BL/6 mouse, male, 6-8 weeks old | FA:0.39 µg/m3; UA:59.75 µg/m3; CAP:483.61 µg/m3 | 6 h/d,5 d/周,共5周 | 精子活力降低[ |
C57BL/6小鼠,雄性,6周龄 C57BL/6 mouse, male, 6 weeks old | UA:94.84 µg/m3; CAP:900.21 µg/m3 | 6 h/d,分别暴露8周和16周 | 精子数量减少,活力降低,睾丸支持细胞空泡化,生精细胞变性[ |
C57BL/6小鼠,雄性,8周龄 C57BL/6 mouse, male, 8 weeks old | FA:0 µg/m3; CAP:75.78 µg/m3 | 60 d | 子代出生数量减少,睾丸重量减轻,精子数量减少,睾酮水平下降[ |
C57BL/6小鼠,雄性,8周龄 C57BL/6 mouse, male, 8 weeks old | FA:4.5 µg/m3; CAP:72.26 µg/m3 | 8 h/d,5 d/周,连续暴露16周 | 精子数量减少,精子活力下降,睾酮水平下降[ |
SD大鼠,雄性,6周龄 SD rat, male, 6 weeks old | FA:0.70 µg/m3; CAP:16.7 µg/m3 | 暴露8个月 | 睾丸内脂质紊乱[ |
Wistar大鼠,雄性,6周龄 Wistar rat, male, 6 weeks old | 对照组:0.02~0.18 mg/m3; 4倍浓缩组:0.06~0.81 mg/m3; 8倍浓缩组:0.11~1.60 mg/m3 | 8 h/d,连续3个月 | 间质水肿,生精精管细胞层次减少,各级生精细胞排列紊乱甚至缺失[ |
C57BL/6小鼠,雌性,8周龄 C57BL/6 mouse, female, 8 weeks old | FA:2.4 µg/m3; CAP:49.4 µg/m3 | 孕前每天暴露12 h,7 d/周,暴露4周,孕期继续暴露直到子代出生 | 母代卵巢储备降低,子代小鼠在出生后第3天和出生后第7天的原始卵泡和总卵泡数量均减少[ |
C57BL/6小鼠,雌性,4月龄 C57BL/6 mouse, female, 4 months old | FA:<5 µg/m3; CAP:110~130 µg/m3 | 5 h/d,4 h/周,持续12周 | 生长卵泡凋亡,卵巢储备降低[ |
C57BL/6小鼠,雌性,4周龄 C57BL/6 mouse, female, 4 weeks old | FA:3.93 µg/m3; CAP:128.1 µg/m3 | 8 h/d,5 d/周,共9周 | 卵巢闭锁[ |
动物模型 Animal model | PM2.5暴露浓度 Exposure concentration of PM2.5 | PM2.5暴露时间 Exposure duration of PM2.5 | 生殖毒性相关表型 Associated phenotypes of reproductive toxicity |
---|---|---|---|
C57BL/6小鼠,雌性,8周龄 C57BL/6 mouse, female, 8 weeks old | 低剂量组:4.8 mg/kg; 高剂量组:43.2 mg/kg | 孕期每3 d 1次,共滴注6次 | F1代精子数量和活力下降,畸形率增加;支持细胞形态异常,精子发生异常[ |
C57BL/6 小鼠,雄性,5周龄 C57BL/6 mouse, male, 5 weeks old | 1.0 mg/kg | 每周一、三、五暴露,共29周 | 生育能力下降,精子数量和活力明显降低[ |
SD大鼠,雄性,8周龄 SD rat, male, 8 weeks old | 低剂量组:4.3 mg/kg; 高剂量组:12.9 mg/kg | 每2 d 1次,共滴注4周 | 睾丸重量及睾丸系数减低,曲细精管管壁变薄,各级生精细胞排列松散紊乱,管腔中成熟精子数量减少,睾酮水平下降[ |
SD大鼠,雄性,4周龄 SD rat, male, 4 weeks old | 1.5 mg/kg | 每周5 d,共4周 | 精子质量和血清睾酮水平显著降低。生精细胞结构松散,生精细胞和成熟精子的数量减少[ |
SD大鼠,雄性,6周龄 SD rat, male, 6 weeks old | 低剂量组:10 mg/kg; 高剂量组:20 mg/kg | 每天1次,共4周 | 精子质量降低,睾丸血睾屏障损伤,生育力降低[ |
SD大鼠,雄性,8周龄 SD rat, male, 8 weeks old | 25 mg/kg | 每周1次,连续3个月 | 睾丸代谢组紊乱[ |
SD大鼠,雄性,6~8周龄 SD rat, male, 6-8 weeks old | 低剂量组:1.8 mg/kg; 中剂量组:5.4 mg/kg; 高剂量组:16.2 mg/kg | 每3 d 1次,共30 d | 精子存活率和密度显著降低,畸形率显著增加,睾酮和促黄体生成素水平下降,血睾屏障的超微结构发生改变[ |
SD大鼠,雄性,6周龄 SD rat, male, 6 weeks old | 低剂量组:9 mg/kg; 高剂量组:24 mg/kg | 每天1次,共7周 | 大鼠生育力明显降低,精子数量显著减少,精子畸形率增加,睾丸组织形态损伤,生精细胞减少并脱落,生精小管直径减少[ |
SD大鼠,雄性,180~220 g SD rat, male, 180-220 g | 夏季:0.2、0.6、1.5 mg/kg; 冬季:0.3、1.5、2.7 mg/kg | 每3 d 1次,共2个月 | 睾丸组织损伤,睾丸生殖细胞凋亡[ |
SD大鼠,雄性,4周龄 SD rat, male, 4 weeks old | 低剂量组:20 µg/kg; 高剂量组:160 µg/kg | 每天1次,连续60 d | 精子数量和质量明显下降,生精小管结构紊乱,管腔精子数减少[ |
昆明小鼠,雌性,6~7 周龄 Kunming mouse, female, 6 to 7 weeks old | 低剂量组:0.259 2 µg/µL; 中剂量组:1.566 95 µg/µL; 高剂量组:3.456 µg/µL | 妊娠第1天开始 每3 d 1 次,孕期暴露7 次 | 孕鼠体重增长缓慢,妊娠天数减少[ |
昆明小鼠,雌性,4周龄 Kunming mouse, female, 4 weeks old | 低剂量组:0.36 µg/µL; 中剂量组:1.2 µg/µL; 高剂量组:2.4 µg/µL | 每3 d 1次,共4周 | 窝仔数减少,颗粒细胞核膜、染色体和线粒体超微结构改变,囊胚形成率低[ |
SD大鼠,雌性,成年 SD rat, female, adult | 低剂量组:0.5 mg/kg; 中剂量组:2 mg/kg; 高剂量组:8 mg/kg | 孕前滴注15 d,孕期6 d,每天1次 | 雌鼠的交配指数及GD6.5受孕指数下降,胚胎个数减少,子宫连胚质量下降[ |
SD大鼠,雌性,8周龄 SD rat, female, 8 weeks old | 低剂量组:1.5 mg/kg; 高剂量组:6 mg/kg | 每天1次,连续30 d | 子宫脏器系数、内膜上皮细胞厚度和腺上皮高度增加[ |
C57BL/6,雌性 C57BL/6, female | 3 mg/kg | 孕期每隔1 d滴注1次 | 胎盘细胞增殖受到抑制,胎盘营养物质的运输能力受损[ |
ICR小鼠,雌性,成年 ICR mouse, female, adult | 对照组:1 mL/kg; PM2.5组:15 mg/kg | 妊娠期第3、6、9、12、15天及哺乳期第5、10、15天滴注 | F1 代小鼠体重下降或体重增长缓慢,且具有跨代遗传效应,并可能通过F2代生殖系统传递给子F3代小鼠[ |
ICR小鼠,雌性,4周龄 ICR mouse, female, 4 weeks old | 10 mg/kg | 鼻内滴注,每2 d最多滴注11次,连续3周 | 卵巢组织出血和血管出血,卵泡细胞凋亡增加[ |
表2 用于生殖毒性研究的PM2.5滴注暴露模型的造模方法和相关表型
Table 2 Modeling methods and associated phenotypes of PM2.5 instillation exposure models for reproductive toxicity studies
动物模型 Animal model | PM2.5暴露浓度 Exposure concentration of PM2.5 | PM2.5暴露时间 Exposure duration of PM2.5 | 生殖毒性相关表型 Associated phenotypes of reproductive toxicity |
---|---|---|---|
C57BL/6小鼠,雌性,8周龄 C57BL/6 mouse, female, 8 weeks old | 低剂量组:4.8 mg/kg; 高剂量组:43.2 mg/kg | 孕期每3 d 1次,共滴注6次 | F1代精子数量和活力下降,畸形率增加;支持细胞形态异常,精子发生异常[ |
C57BL/6 小鼠,雄性,5周龄 C57BL/6 mouse, male, 5 weeks old | 1.0 mg/kg | 每周一、三、五暴露,共29周 | 生育能力下降,精子数量和活力明显降低[ |
SD大鼠,雄性,8周龄 SD rat, male, 8 weeks old | 低剂量组:4.3 mg/kg; 高剂量组:12.9 mg/kg | 每2 d 1次,共滴注4周 | 睾丸重量及睾丸系数减低,曲细精管管壁变薄,各级生精细胞排列松散紊乱,管腔中成熟精子数量减少,睾酮水平下降[ |
SD大鼠,雄性,4周龄 SD rat, male, 4 weeks old | 1.5 mg/kg | 每周5 d,共4周 | 精子质量和血清睾酮水平显著降低。生精细胞结构松散,生精细胞和成熟精子的数量减少[ |
SD大鼠,雄性,6周龄 SD rat, male, 6 weeks old | 低剂量组:10 mg/kg; 高剂量组:20 mg/kg | 每天1次,共4周 | 精子质量降低,睾丸血睾屏障损伤,生育力降低[ |
SD大鼠,雄性,8周龄 SD rat, male, 8 weeks old | 25 mg/kg | 每周1次,连续3个月 | 睾丸代谢组紊乱[ |
SD大鼠,雄性,6~8周龄 SD rat, male, 6-8 weeks old | 低剂量组:1.8 mg/kg; 中剂量组:5.4 mg/kg; 高剂量组:16.2 mg/kg | 每3 d 1次,共30 d | 精子存活率和密度显著降低,畸形率显著增加,睾酮和促黄体生成素水平下降,血睾屏障的超微结构发生改变[ |
SD大鼠,雄性,6周龄 SD rat, male, 6 weeks old | 低剂量组:9 mg/kg; 高剂量组:24 mg/kg | 每天1次,共7周 | 大鼠生育力明显降低,精子数量显著减少,精子畸形率增加,睾丸组织形态损伤,生精细胞减少并脱落,生精小管直径减少[ |
SD大鼠,雄性,180~220 g SD rat, male, 180-220 g | 夏季:0.2、0.6、1.5 mg/kg; 冬季:0.3、1.5、2.7 mg/kg | 每3 d 1次,共2个月 | 睾丸组织损伤,睾丸生殖细胞凋亡[ |
SD大鼠,雄性,4周龄 SD rat, male, 4 weeks old | 低剂量组:20 µg/kg; 高剂量组:160 µg/kg | 每天1次,连续60 d | 精子数量和质量明显下降,生精小管结构紊乱,管腔精子数减少[ |
昆明小鼠,雌性,6~7 周龄 Kunming mouse, female, 6 to 7 weeks old | 低剂量组:0.259 2 µg/µL; 中剂量组:1.566 95 µg/µL; 高剂量组:3.456 µg/µL | 妊娠第1天开始 每3 d 1 次,孕期暴露7 次 | 孕鼠体重增长缓慢,妊娠天数减少[ |
昆明小鼠,雌性,4周龄 Kunming mouse, female, 4 weeks old | 低剂量组:0.36 µg/µL; 中剂量组:1.2 µg/µL; 高剂量组:2.4 µg/µL | 每3 d 1次,共4周 | 窝仔数减少,颗粒细胞核膜、染色体和线粒体超微结构改变,囊胚形成率低[ |
SD大鼠,雌性,成年 SD rat, female, adult | 低剂量组:0.5 mg/kg; 中剂量组:2 mg/kg; 高剂量组:8 mg/kg | 孕前滴注15 d,孕期6 d,每天1次 | 雌鼠的交配指数及GD6.5受孕指数下降,胚胎个数减少,子宫连胚质量下降[ |
SD大鼠,雌性,8周龄 SD rat, female, 8 weeks old | 低剂量组:1.5 mg/kg; 高剂量组:6 mg/kg | 每天1次,连续30 d | 子宫脏器系数、内膜上皮细胞厚度和腺上皮高度增加[ |
C57BL/6,雌性 C57BL/6, female | 3 mg/kg | 孕期每隔1 d滴注1次 | 胎盘细胞增殖受到抑制,胎盘营养物质的运输能力受损[ |
ICR小鼠,雌性,成年 ICR mouse, female, adult | 对照组:1 mL/kg; PM2.5组:15 mg/kg | 妊娠期第3、6、9、12、15天及哺乳期第5、10、15天滴注 | F1 代小鼠体重下降或体重增长缓慢,且具有跨代遗传效应,并可能通过F2代生殖系统传递给子F3代小鼠[ |
ICR小鼠,雌性,4周龄 ICR mouse, female, 4 weeks old | 10 mg/kg | 鼻内滴注,每2 d最多滴注11次,连续3周 | 卵巢组织出血和血管出血,卵泡细胞凋亡增加[ |
1 | RISK FACTORS COLLABORATORS GBD. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet, 2024, 403(10440):2162-2203. DOI: 10.1016/S0140-6736(24)00933-4 . |
2 | THANGAVEL P, PARK D, LEE Y C. Recent insights into particulate matter (PM2.5)-mediated toxicity in humans: an overview[J]. Int J Environ Res Public Health, 2022, 19(12):7511. DOI: 10.3390/ijerph19127511 . |
3 | ZHENG S K, ZHAO N N, LIN X J, et al. Impacts and potential mechanisms of fine particulate matter (PM2.5) on male testosterone biosynthesis disruption[J/OL]. Rev Environ Health, 2023, Sep 1. https://pubmed.ncbi.nlm.nih.gov/37651650/. DOI: 10.1515/reveh-2023-0064 . |
4 | WANG L J, LUO D, LIU X L, et al. Effects of PM2.5 exposure on reproductive system and its mechanisms[J]. Chemosphere, 2021, 264(Pt 1):128436. DOI: 10.1016/j.chemosphere. 2020. 128436 . |
5 | LIAO B Q, LIU C B, XIE S J, et al. Effects of fine particulate matter (PM2.5) on ovarian function and embryo quality in mice[J]. Environ Int, 2020, 135:105338. DOI: 10.1016/j.envint.2019.105338 . |
6 | ZHOU L X, SU X, LI B H, et al. PM2.5 exposure impairs sperm quality through testicular damage dependent on NALP3 inflammasome and miR-183/96/182 cluster targeting FOXO1 in mouse[J]. Ecotoxicol Environ Saf, 2019, 169:551-563. DOI: 10.1016/j.ecoenv.2018.10.108 . |
7 | WEI X Y, ZHANG Z H, GU Y Y, et al. Inter- and trans-generational impacts of real-world PM2.5 exposure on male-specific primary hypogonadism[J]. Cell Discov, 2024, 10(1):44. DOI: 10.1038/s41421-024-00657-0 . |
8 | 周逢海, 周川, 吕海迪, 等. 细颗粒物对雄性小鼠生殖功能的影响[J]. 海南医学, 2019, 30(5):545-548. DOI: 10.3969/j.issn.1003-6350.2019.05.001 . |
ZHOU F H, ZHOU C, LV H D, et al. Effect of fine particles on reproductive function of male mice[J]. J Hainan Med Univ, 2019, 30(5):545-548. DOI: 10.3969/j.issn.1003-6350.2019.05.001 . | |
9 | LUDERER U, LIM J, ORTIZ L, et al. Exposure to environmentally relevant concentrations of ambient fine particulate matter (PM2.5) depletes the ovarian follicle reserve and causes sex-dependent cardiovascular changes in apolipoprotein E null mice[J]. Part Fibre Toxicol, 2022, 19(1):5. DOI: 10.1186/s12989-021-00445-8 . |
10 | LIN C Y, CHEN W L, CHEN T Z, et al. Lipid changes in extrapulmonary organs and serum of rats after chronic exposure to ambient fine particulate matter[J]. Sci Total Environ, 2021, 784:147018. DOI: 10.1016/j.scitotenv.2021.147018 . |
11 | 丁素素, 刘焕亮, 林本成, 等. PM2.5长期动态低浓度恒定及高浓度间隔吸入暴露对雄性大鼠睾丸的损伤效应[J]. 环境与健康杂志, 2020, 37(1):11-15, 封2. DOI: 10.16241/j.cnki.1001-5914.2020.01.003 . |
DING S S, LIU H L, LIN B C, et al. Effects of long-term dynamic inhalation of PM2.5 with constant low concentration and interval high concentration on testis damage in male rats[J]. J Environ Health, 2020, 37(1):11-15, second cover page. DOI: 10.16241/j.cnki.1001-5914.2020.01.003 . | |
12 | CHEN L C, LIPPMANN M. Inhalation toxicology methods: the generation and characterization of exposure atmospheres and inhalational exposures[J]. Curr Protoc Toxicol, 2015, 63:24.4.1-24.424.4.23. DOI: 10.1002/0471140856.tx2404s63 . |
13 | CAO X W, WANG M, LI J W, et al. Fine particulate matter increases airway hyperresponsiveness through kallikrein-bradykinin pathway[J]. Ecotoxicol Environ Saf, 2020, 195:110491. DOI: 10.1016/j.ecoenv.2020.110491 . |
14 | FENG S, DUAN E H, SHI X J, et al. Hydrogen ameliorates lung injury in a rat model of subacute exposure to concentrated ambient PM2.5 via Aryl hydrocarbon receptor[J]. Int Immunopharmacol, 2019, 77:105939. DOI: 10.1016/j.intimp.2019.105939 . |
15 | PAULUHN J. Overview of testing methods used in inhalation toxicity: from facts to artifacts[J]. Toxicol Lett, 2003, 140-141:183-193. DOI: 10.1016/s0378-4274(02)00509-x . |
16 | OYABU T, MORIMOTO Y, IZUMI H, et al. Comparison between whole-body inhalation and nose-only inhalation on the deposition and health effects of nanoparticles[J]. Environ Health Prev Med, 2016, 21(1):42-48. DOI: 10.1007/s12199-015-0493-z . |
17 | KOGEL U, WONG E T, SZOSTAK J, et al. Impact of whole-body versus nose-only inhalation exposure systems on systemic, respiratory, and cardiovascular endpoints in a 2-month cigarette smoke exposure study in the ApoE-/- mouse model[J]. J Appl Toxicol, 2021, 41(10):1598-1619. DOI: 10.1002/jat.4149 . |
18 | WANG J K, ZHANG Z H, SHI F Q, et al. PM2.5 caused ferroptosis in spermatocyte via overloading iron and disrupting redox homeostasis[J]. Sci Total Environ, 2023, 872:162089. DOI: 10.1016/j.scitotenv.2023.162089 . |
19 | SHI F Q, ZHANG Z H, WANG J K, et al. Analysis by metabolomics and transcriptomics for the energy metabolism disorder and the aryl hydrocarbon receptor activation in male reproduction of mice and GC-2spd cells exposed to PM2.5 [J]. Front Endocrinol, 2021, 12:807374. DOI: 10.3389/fendo.2021.807374 . |
20 | ZHENG S K, JIANG J C, SHU Z H, et al. Fine particulate matter (PM2.5) induces testosterone disruption by triggering ferroptosis through SIRT1/HIF-1α signaling pathway in male mice[J]. Free Radic Biol Med, 2024, 221:40-51. DOI: 10.1016/j.freeradbiomed.2024.05.026 . |
21 | CHEN Y Y, XI Y Y, LI M L, et al. Maternal exposure to PM2.5 decreases ovarian reserve in neonatal offspring mice through activating PI3K/AKT/FoxO3a pathway and ROS-dependent NF-κB pathway[J]. Toxicology, 2022, 481:153352. DOI: 10.1016/j.tox.2022.153352 . |
22 | YANG M J, TIAN F, TAO S M, et al. Concentrated ambient fine particles exposure affects ovarian follicle development in mice[J]. Ecotoxicol Environ Saf, 2022, 231:113178. DOI: 10.1016/j.ecoenv.2022.113178 . |
23 | WANG H Y, WANG T H, RUI W, et al. Extracellular vesicles enclosed-miR-421 suppresses air pollution (PM2.5)-induced cardiac dysfunction via ACE2 signalling[J]. J Extracell Vesicles, 2022, 11(5): e12222. DOI: 10.1002/jev2.12222 . |
24 | SMYTH T, VEAZEY J, ELISEEVA S, et al. Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin[J]. Part Fibre Toxicol, 2020, 17(1):52. DOI: 10.1186/s12989-020-00383-x . |
25 | MORIMOTO Y, IZUMI H, YOSHIURA Y, et al. Usefulness of intratracheal instillation studies for estimating nanoparticle-induced pulmonary toxicity[J]. Int J Mol Sci, 2016, 17(2):165. DOI: 10.3390/ijms17020165 . |
26 | MORIMOTO Y, IZUMI H, YOSHIURA Y, et al. Significance of intratracheal instillation tests for the screening of pulmonary toxicity of nanomaterials[J]. J UOEH, 2017, 39(2):123-132. DOI: 10.7888/juoeh.39.123 . |
27 | ZHU N, JI X T, GENG X L, et al. Maternal PM2.5 exposure and abnormal placental nutrient transport[J]. Ecotoxicol Environ Saf, 2021, 207:111281. DOI: 10.1016/j.ecoenv.2020.111281 . |
28 | 张丰泉, 董恩恒, 王茂, 等. PM2.5对雌鼠生殖内分泌水平和妊娠结局的影响[J]. 中国实验动物学报, 2017, 25(4):455-460. DOI: 10.3969/j.issn.1005-4847.2017.04.019 . |
ZHANG F Q, DONG E H, WANG M, et al. Effects of PM2.5 on reproductive hormone levels and pregnancy outcome in female rats[J]. Acta Lab Animalis Sci Sin, 2017, 25(4):455-460. DOI: 10.3969/j.issn.1005-4847.2017.04.019 . | |
29 | 张丰泉, 赵杉, 董恩恒. PM2.5通过激活NLRP3/Caspse-1通路诱导大鼠子宫炎症反应[J]. 中国生物化学与分子生物学报, 2022, 38(9):1234-1241. DOI: 10.13865/j.cnki.cjbmb.2022.07.1064 . |
ZHANG F Q, ZHAO S, DONG E H. PM2.5 induces uterine inflammation via activating of NLRP3/caspse-1 pathway[J]. Chin J Biochem Mol Biol, 2022, 38(9):1234-1241. DOI: 10.13865/j.cnki.cjbmb.2022.07.1064 . | |
30 | 张丰泉, 赵杉, 董恩恒, 等. 核转录因子NF-E2相关因子2信号通路在PM2.5致雌性大鼠生殖损伤中的作用[J]. 中国实验动物学报, 2018, 26(5):639-643. DOI: 10.3969/j.issn.1005-4847.2018.05.016 . |
ZHANG F Q, ZHAO S, DONG E H, et al. Effect of NF-E2 related factor 2 pathway activation on PM2.5 induced reproductive injury in female rats[J]. Acta Lab Animalis Sci Sin, 2018, 26(5):639-643. DOI: 10.3969/j.issn.1005-4847.2018.05.016 . | |
31 | 邱娴娴, 安妮妮, 江克华, 等. PM2.5暴露通过NF-κB信号通路致雄性大鼠生殖功能障碍[J]. 实用医学杂志, 2022, 38(7):836-840, 847. DOI: 10.3969/j.issn.1006-5725.2022.07.011 . |
QIU X X, AN N N, JIANG K H, et al. Reproductive dysfunction induced by PM2.5 exposure through NF-κB signaling pathway in male rats[J]. J Pract Med, 2022, 38(7):836-840, 847. DOI: 10.3969/j.issn.1006-5725.2022.07.011 . | |
32 | LIU X N, JIN X T, SU R J, et al. The reproductive toxicology of male SD rats after PM2.5 exposure mediated by the stimulation of endoplasmic reticulum stress[J]. Chemosphere, 2017, 189:547-555. DOI: 10.1016/j.chemosphere.2017.09.082 . |
33 | 王婷婷, 郑昕蕊, 李文燕, 等. 母源性PM2.5暴露致子代鼠大脑皮层神经炎症与星形胶质细胞和小胶质细胞激活[J]. 中国组织化学与细胞化学杂志, 2018, 27(4):313-320. DOI: 10.16705/j.cnki.1004-1850.2018.04.002 . |
WANG T T, ZHENG X R, LI W Y, et al. Maternal PM2.5 exposure induces the activation of astrocytes and microglia and subsequent neuroinflammation in the cerebral cortex in mouse offspring[J]. Chin J Histochem Cytochem, 2018, 27(4):313-320. DOI: 10.16705/j.cnki.1004-1850.2018.04.002 . | |
34 | 赵会, 谭金峰, 刘德文, 等. 妊娠期大气细颗粒物暴露损伤孕鼠多种器官并抑制妊娠及胎儿发育[J]. 中国组织化学与细胞化学杂志, 2016, 25(1):42-48. DOI: 10.16705/j.cnki.1004-1850.2016.01.008 . |
ZHAO H, TAN J F, LIU D W, et al. Exposure to Atmospheric fine particulate matter damages multiple organs of pregnant mice and inhibits pregnancy and fetal development during pregnancy[J]. Chin J Histochem Cytochem, 2016, 25(1):42-48. DOI: 10.16705/j.cnki.1004-1850.2016.01.008 . | |
35 | 余伊翔, 曹珊珊, 冯怡, 等. 大鼠气管滴注方法的改良及效果评价[J]. 实验动物与比较医学, 2021, 41(6): 543-546. DOI: 10.12300/j.issn.1674-5817.2021.031 . |
YU Y X, CAO S S, FENG Y, et al. Improvement and effect evaluation on method of tracheal instillation in rats[J]. Lab Anim Comp Med, 2021, 41(6): 543-546. DOI: 10.12300/j.issn.1674-5817.2021.031 . | |
36 | LIU X M, GE P X, LU Z Y, et al. Reproductive toxicity and underlying mechanisms of fine particulate matter (PM2.5) on Caenorhabditis elegans in different seasons[J]. Ecotoxicol Environ Saf, 2022, 248:114281. DOI: 10.1016/j.ecoenv. 2022. 114281 . |
37 | YANG R Y, GE P X, LIU X M, et al. Chemical composition and transgenerational effects on Caenorhabditis elegans of seasonal fine particulate matter[J]. Toxics, 2023, 11(2):116. DOI: 10.3390/toxics11020116 . |
38 | RHEE J, HAN E, NAM K J, et al. Assessment of hair cell damage and developmental toxicity after fine particulate matter 2.5 μm (PM2.5) exposure using zebrafish (Danio rerio) models[J]. Int J Pediatr Otorhinolaryngol, 2019, 126:109611. DOI: 10.1016/j.ijporl.2019.109611 . |
39 | HUANG J, LU H, DU J W, et al. Effects of exposure to PM2.5 during pregnancy on the multigenerational reproductive outcomes of male mouse offspring and the role of Sertoli cells[J]. Environ Sci Pollut Res Int, 2023, 30(47):103823-103835. DOI: 10.1007/s11356-023-29751-8 . |
40 | YANG W, XU Y Y, PAN H J, et al. Chronic exposure to diesel exhaust particulate matter impairs meiotic progression during spermatogenesis in a mouse model[J]. Ecotoxicol Environ Saf, 2020, 202:110881. DOI: 10.1016/j.ecoenv. 2020. 110881 . |
41 | YANG Y, FENG Y J, HUANG H, et al. PM2.5 exposure induces reproductive injury through IRE1/JNK/autophagy signaling in male rats[J]. Ecotoxicol Environ Saf, 2021, 211:111924. DOI: 10.1016/j.ecoenv.2021.111924 . |
42 | LIU B, WU S D, SHEN L J, et al. Spermatogenesis dysfunction induced by PM2.5 from automobile exhaust via the ROS-mediated MAPK signaling pathway[J]. Ecotoxicol Environ Saf, 2019, 167:161-168. DOI: 10.1016/j.ecoenv.2018.09.118 . |
43 | CAO X N, SHEN L J, WU S D, et al. Urban fine particulate matter exposure causes male reproductive injury through destroying blood-testis barrier (BTB) integrity[J]. Toxicol Lett, 2017, 266:1-12. DOI: 10.1016/j.toxlet.2016.12.004 . |
44 | 王晓飞, 蒋守芳, 张维冰, 等. 利用代谢组学研究大气细颗粒物的生殖毒性效应[J]. 分析化学, 2017, 45(5):633-640. DOI: 10.11895/j.issn.0253-3820.170020 . |
WANG X F, JIANG S F, ZHANG W B, et al. Study on reproductive toxicity of fine particulate matter by metabolomics[J]. Chin J Anal Chem, 2017, 45(5):633-640. DOI: 10.11895/j.issn.0253-3820.170020 . | |
45 | ZHANG J, LIU J H, REN L H, et al. PM2.5 induces male reproductive toxicity via mitochondrial dysfunction, DNA damage and RIPK1 mediated apoptotic signaling pathway[J]. Sci Total Environ, 2018, 634:1435-1444. DOI: 10.1016/j.scitotenv.2018.03.383 . |
46 | LIU J H, REN L H, WEI J L, et al. Fine particle matter disrupts the blood-testis barrier by activating TGF-β3/p38 MAPK pathway and decreasing testosterone secretion in rat[J]. Environ Toxicol, 2018, 33(7):711-719. DOI: 10.1002/tox.22556 . |
47 | WEI Y, CAO X N, TANG X L, et al. Urban fine particulate matter (PM2.5) exposure destroys blood-testis barrier (BTB) integrity through excessive ROS-mediated autophagy[J]. Toxicol Mech Methods, 2018, 28(4):302-319. DOI: 10.1080/15376516.2017.1410743 . |
48 | 严超, 曹希宁, 沈炼桔, 等. 汽车尾气来源PM2.5颗粒物长期暴露导致SD雄鼠生殖功能损害[J]. 中华男科学杂志, 2016, 22(2):104-109. DOI: 10.13263/j.cnki.nja.2016.02.002 . |
YAN C, CAO X N, SHEN L J, et al. Long-term exposure to PM2.5 from automobile exhaust results in reproductive dysfunction in male rats[J]. Natl J Androl, 2016, 22(2):104-109. DOI: 10.13263/j.cnki.nja.2016.02.002 . | |
49 | 吴思雨, 侯海燕, 张利文, 等. 大气细颗粒物PM2.5对雌性大鼠生育力损伤作用的研究[J]. 国际妇产科学杂志, 2016, 43(3):258-262. |
WU S Y, HOU H Y, ZHANG L W, et al. Impairment of airborne fine particulate matters PM2.5 to the fertility of female rats[J]. J Int Obstet Gynecol, 2016, 43(3):258-262. | |
50 | 周雅琳, 张敏佳, 刘伟, 等. 孕期及哺乳期PM2.5暴露致子代小鼠低体重的跨代遗传效应[J]. 环境与健康杂志, 2019, 36(2):111-115. DOI: 10.16241/j.cnki.1001-5914.2019.02.005 . |
ZHOU Y L, ZHANG M J, LIU W, et al. Transgenerational effects of offspring low body weight induced by maternal exposure to PM2.5 during pregnancy and lactation[J]. J Environ Health, 2019, 36(2):111-115. DOI: 10.16241/j.cnki.1001-5914.2019.02.005 . | |
51 | GAI H F, AN J X, QIAN X Y, et al. Ovarian damages produced by aerosolized fine particulate matter (PM2.5) pollution in mice: possible protective medications and mechanisms[J]. Chin Med J, 2017, 130(12):1400-1410. DOI: 10.4103/0366-6999.207472 . |
52 | 杨阳, 刘福荣, 崔留欣, 等. PM2.5暴露对雄性大鼠生殖功能及IRE1-JNK通路相关蛋白表达的影响[J]. 郑州大学学报(医学版), 2021, 56(3):309-313. DOI: 10.13705/j.issn.1671-6825.2020.04.024 . |
YANG Y, LIU F R, CUI L X, et al. Effects of PM2.5 exposure on reproductive function and expressions of IRE1-JNK pathway related proteins in male rats[J]. J Zhengzhou Univ Med Sci, 2021, 56(3):309-313. DOI: 10.13705/j.issn.1671-6825.2020.04.024 . | |
53 | CHENG C Y, WONG E W, LIE P P, et al. Regulation of blood-testis barrier dynamics by desmosome, gap junction, hemidesmosome and polarity proteins: an unexpected turn of events[J]. Spermatogenesis, 2011, 1(2):105-115. DOI: 10.4161/spmg.1.2.15745 . |
54 | MESQUITA S R, VAN DROOGE B L, OLIVEIRA E, et al. Differential embryotoxicity of the organic pollutants in rural and urban air particles[J]. Environ Pollut, 2015, 206:535-542. DOI: 10.1016/j.envpol.2015.08.008 . |
55 | GASKINS A J, MÍNGUEZ-ALARCÓN L, FONG K C, et al. Exposure to fine particulate matter and ovarian reserve among women from a fertility clinic[J]. Epidemiology, 2019, 30(4):486-491. DOI: 10.1097/EDE.0000000000001029 . |
56 | YUAN L, ZHANG Y, WANG W D, et al. Critical windows for maternal fine particulate matter exposure and adverse birth outcomes: the Shanghai birth cohort study[J]. Chemosphere, 2020, 240:124904. DOI: 10.1016/j.chemosphere.2019.124904 . |
57 | 巩艳, 李文燕, 郑昕蕊, 等. 妊娠期大气细颗粒物暴露对新生小鼠肝脏发育的影响[J]. 中国组织化学与细胞化学杂志, 2016, 25(5):406-410. DOI: 10.16705/j.cnki.1004-1850.2016.05.005 . |
GONG Y, LI W Y, ZHENG X R, et al. Effects of gestational exposure to atmospheric fine particulate matter on liver development of newborn mice[J]. Chin J Histochem Cytochem, 2016, 25(5):406-410. DOI: 10.16705/j.cnki.1004-1850.2016.05.005 . |
[1] | 杨家豪, 丁纯蕾, 钱风华, 孙旗, 姜旭升, 陈雯, 沈梦雯. 脓毒症相关脏器损伤动物模型研究进展[J]. 实验动物与比较医学, 2024, 44(6): 636-644. |
[2] | 孙效容, 苏丹, 贵文娟, 陈玥. 手术诱导大鼠中重度膝骨关节炎模型的建立与评价[J]. 实验动物与比较医学, 2024, 44(6): 597-604. |
[3] | 赵小娜, 王鹏, 叶茂青, 曲新凯. 应用Triacsin C构建新型高血糖肥胖小鼠心功能减退模型[J]. 实验动物与比较医学, 2024, 44(6): 605-612. |
[4] | 涂颖欣, 纪依澜, 王菲, 杨东明, 王冬冬, 孙芷馨, 戴悦欣, 王言吉, 阚广捍, 吴斌, 赵德明, 杨利峰. 小型猪后肢去负荷模拟失重模型的建立与组织损伤研究[J]. 实验动物与比较医学, 2024, 44(5): 475-486. |
[5] | 黄冬妍, 吴建辉. 生殖毒理学研究动物模型的建立方法及应用评价[J]. 实验动物与比较医学, 2024, 44(5): 550-559. |
[6] | 郑艺清, 邓亚胜, 范燕萍, 梁天薇, 黄慧, 刘永辉, 倪召兵, 林江. 基于数据挖掘的盆腔炎性疾病动物模型应用分析[J]. 实验动物与比较医学, 2024, 44(4): 405-418. |
[7] | 吴玥, 李璐, 张阳, 王珏, 冯婷婷, 李依桐, 王凯, 孔琪. 冠状病毒感染动物模型组学数据集成分析[J]. 实验动物与比较医学, 2024, 44(4): 357-373. |
[8] | 丁天送, 谢京红, 杨斌, 李河桥, 乔一倬, 陈心如, 田纹凡, 李佳佩, 张婉怡, 李帆旋. 复发性流产动物模型特点评价与应用分析[J]. 实验动物与比较医学, 2024, 44(4): 393-404. |
[9] | 姚广源, 董平, 吴昊, 柏梅, 党嬴, 王悦, 胡凯. 长骨骨折动物模型的研究进展[J]. 实验动物与比较医学, 2024, 44(3): 289-296. |
[10] | 包方奇, 屠海烨, 方明笋, 张倩, 陈民利. 基于动物模型的高尿酸肾病病理及分子机制研究进展[J]. 实验动物与比较医学, 2024, 44(2): 180-191. |
[11] | 张莉, 匡宇, 韩凌霞. 人与其他动物椎间盘解剖和组织学结构的比较医学研究进展[J]. 实验动物与比较医学, 2024, 44(2): 192-201. |
[12] | 梁天薇, 邓亚胜, 黄慧, 荣娜, 刘鑫, 王玉洁, 林江. 围绝经期综合征动物模型的制备方法及评价指标分析[J]. 实验动物与比较医学, 2024, 44(1): 74-84. |
[13] | . 自发性脑出血动物模型选择及临床前药物试验指南(2024年版)[J]. 实验动物与比较医学, 2024, 44(1): 3-30. |
[14] | 刘欣, 石少波, 张翠, 杨波, 曲川. 小鼠自体动静脉内瘘端侧吻合模型的建立与评价[J]. 实验动物与比较医学, 2023, 43(6): 595-603. |
[15] | 万颖寒, 顾也欣, 袁雨浓, 汤忞, 鲁立. FDA现代化法案2.0给疾病动物模型发展带来的启示和思考[J]. 实验动物与比较医学, 2023, 43(5): 472-481. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||