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

doi:10.12300/j.issn.1674-5817.2024.068

Abstract

Abstract:

Atmospheric fine particulate matter (particulate matter 2.5,PM_2.5) 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 PM_2.5 exposure and its underlying mechanisms. This paper, based on recent literature, summarizes current methods for establishing PM_2.5-exposed animal models and the evaluation criteria for reproductive toxicity research. The primary modeling methods for PM_2.5 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 PM_2.5 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 PM_2.5-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 PM_2.5, 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 PM_2.5 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 PM_2.5 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 PM_2.5.

Key words: Atmospheric fine particulate matter, PM_2.5, Reproductive toxicity, Animal model

CLC Number:

R994.6

TIAN Fang,PAN Bin,SHI Jiayi,et al. Advances in Development of PM_2.5-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.

Figures/Tables 2

References 57

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 (PM_2.5)-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 (PM_2.5) 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 (PM_2.5) 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 (PM_2.5) 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 PM_2.5 [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 (PM_2.5) 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 (PM_2.5)-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 PM_2.5 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 (PM_2.5) 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 PM_2.5 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 PM_2.5 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. PM_2.5 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 (PM_2.5) 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 .

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[15]	Shuwu XIE, Ruling SHEN, Jinxing LIN, Chun FAN. Progress in Establishment and Application of Laboratory Animal Models Related to Development of Male Infertility Drugs [J]. Laboratory Animal and Comparative Medicine, 2023, 43(5): 504-511.