生殖毒理学研究动物模型的建立方法及应用评价

doi:10.12300/j.issn.1674-5817.2024.028

实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (5): 550-559.DOI: 10.12300/j.issn.1674-5817.2024.028

生殖毒理学研究动物模型的建立方法及应用评价

黄冬妍¹^,²(), 吴建辉¹^,²()()

^1.上海市生物医药技术研究院, 国家卫生健康委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.上海市生物医药技术研究院药理毒理学研究室, 上海 200032

收稿日期:2024-02-23 修回日期:2024-07-28 出版日期:2024-11-06 发布日期:2024-10-25
通讯作者: 吴建辉（1976—），男，博士，研究员，研究方向：生殖药理毒理学研究。E-mail： wujh_731@163.com。ORCID： 0000-0001-7031-4425
作者简介:黄冬妍（1989—），女，硕士，助理研究员，研究方向：生殖药理毒理学研究。E-mail: hdy043@163.com

Establishment Methods and Application Evaluation of Animal Models in Reproductive Toxicology Research

HUANG Dongyan¹^,²(), WU Jianhui¹^,²()()

^1.Shanghai Institute for Biomedical and Pharmaceutical Technologies, NHC Key Lab of Reproduction Regulation, Shanghai Engineering Research Center of Reproductive Health Drugs and Devices, Shanghai 200237, China
^2.Department of Pharmacology and Toxicology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200032, China

Received:2024-02-23 Revised:2024-07-28 Published:2024-10-25 Online:2024-11-06
Contact: WU Jianhui (ORCID: 0000-0001-7031-4425), E-mail: wujh_731@163.com

摘要/Abstract

摘要：

生殖毒理学是指应用毒理学方法研究外来物质干扰卵子或精子生成的机制及其有害作用对后代影响的学科，研究内容包括受试物对亲代生殖功能的损伤作用和对子代胚胎的毒性评价。人们每天会接触到各种药品、化学品和环境污染物，这些物质是否具有生殖毒性，关乎子孙后代的健康，这就需要通过生殖毒理学研究来进行评价。由于生殖毒性评价的特殊性和重要性，国内外相关机构出台了相应的指导原则、国家标准或行业标准，均涉及动物实验。在生殖系统疾病研究中，目前开发出了很多研究重要生殖器官的动物模型，如睾丸和卵巢研究用动物模型。每种模型均涉及动物的选择、方法的建立和评价指标的量化，且各有其优势和局限性，研究人员使用时要根据试验需求和模型特点来综合考量。本文针对生殖毒理学研究中常用的生殖与发育毒性评价动物模型，包括生育力与早期胚胎发育毒性评价大鼠模型、胚胎-胎仔发育毒性评价大鼠模型、胚胎-胎仔发育毒性评价兔模型、胚胎-胎仔发育毒性评价小型猪模型、围产期毒性评价大鼠模型、胚胎发育毒性评价斑马鱼模型，化学药物和放射疗法诱导、自身免疫性和卵巢切除等方式引起的卵巢毒性评价动物模型，以及化学药物和环境因素引起的睾丸毒性评价动物模型，对这些模型的建立方法、应用范围和特点进行总结，以期为相关领域的研究应用提供参考。

关键词: 生殖毒理学, 发育毒性, 围产期毒性, 睾丸毒性, 卵巢毒性, 动物模型

Abstract:

Reproductive toxicology is a discipline that uses toxicological methods to study the mechanisms by which foreign substances interfere with the generation of eggs or sperm and their detrimental effects on offspring. Research includes evaluating the damaging effects of test substances on reproductive function of parents and the toxicity evaluation of offspring embryos. People are exposed to a wide range of drugs, chemicals and environmental pollutants on a daily basis, and determining whether these substances have reproductive toxicity is crucial for the health of future generations. Reproductive toxicology research is therefore critical. Given the specificity and importance of reproductive toxicity evaluation, corresponding institutions both domestically and internationally have issued guidelines, national standards, or industry standards, all of which involve animal experiments. In the study of reproductive system diseases, numerous animal models have been developed to investigate key reproductive organs, such as testicles and ovaries. Each model involves the selection of animals, the establishment of methods, and the quantification of evaluation indicators, and all have advantages and limitations. The choice of model should be based on experimental needs and the characteristics of the model. This paper summarizes commonly used animal models for reproductive and development toxicity evaluation in reproductive toxicology research, including rat models for fertility and early embryonic development toxicity, rat models for embryo-fetal development toxicity, rabbit models for embryo-fetal development toxicity evaluation, minipig models for embryo-fetal development toxicity, rat models for perinatal toxicity, zebrafish models for embryonic development toxicity, and models for evaluating ovarian toxicity induced by chemical drugs, radiotherapy, autoimmunity, and ovariectomy, as well as models for evaluating testicular toxicity caused by chemical drugs and environmental factors. The methods for establishing these models, their application scope, and characteristics are reviewed in order to provide references for relevant research applications.

Key words: Reproductive toxicology, Development toxicity, Perinatal toxicity, Testicular toxicity, Ovarian toxicity, Animal models

中图分类号:

R994

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. DOI: 10.12300/j.issn.1674-5817.2024.028.

HUANG Dongyan,WU Jianhui. Establishment Methods and Application Evaluation of Animal Models in Reproductive Toxicology Research[J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 550-559. DOI: 10.12300/j.issn.1674-5817.2024.028.

图/表 3

参考文献 42

1	周植星, 陈美灵, 张晓东, 等. 男性生殖系统用药生殖毒性评价的监管要求和关注要点[J]. 中国临床药理学杂志, 2023, 39(21):3183-3192. DOI: 10.13699/j.cnki.1001-6821.2023.21.030 .
	ZHOU Z X, CHEN M L, ZHANG X D, et al. The regulatory requirements and points to consider for the developmental and reproductive toxicity assessment for male reproductive system medicines[J]. Chin J Clin Pharmacol, 2023, 39(21):3183-3192. DOI: 10.13699/j.cnki.1001-6821.2023.21.030 .
2	KIM J H, SCIALLI A R. Thalidomide: the tragedy of birth defects and the effective treatment of disease[J]. Toxicol Sci, 2011, 122(1):1-6. DOI: 10.1093/toxsci/kfr088 .
3	国家药品监督管理局药品审评中心. 药物生殖毒性研究技术指导原则[EB/OL]. (2006-12-19)[2024-02-01]. .
	National Medical Products Administration Drug Evaluation Center. The Technical guidelines for research on reproductive toxicity of drugs[EB/OL]. (2006-12-19)[2024-02 -01 ]. .
4	周萍, 吴建辉. 常见内分泌干扰物对人类生殖功能损伤及其药物干预的研究进展[J]. 中华生殖与避孕杂志, 2022, 42(9):956-961. DOI: 10.3760/cma.j.cn101441-20210307-00106 .
	ZHOU P, WU J H. Research progress on the damage of human reproductive function caused by common endocrine disruptors and its drug intervention[J]. Chin J Reprod Contracept, 2022, 42(9):956-961. DOI: 10.3760/cma.j.cn101441-20210307-00106 .
5	WANG K Y, HUANG D Y, ZHOU P, et al. Bisphenol A exposure triggers the malignant transformation of prostatic hyperplasia in beagle dogs via cfa-miR-204/KRAS axis[J]. Ecotoxicol Environ Saf, 2022, 235:113430. DOI: 10.1016/j.ecoenv.2022.113430 .
6	ZHOU P, WU S S, HUANG D Y, et al. Oral exposure to DEHP may stimulate prostatic hyperplasia associated with upregulation of COX-2 and L-PGDS expressions in male adult rats[J]. Reprod Toxicol, 2022, 112:160-170. DOI: 10.1016/j.reprotox.2022.07.008 .
7	Food and Drug Administration. S5(R3): Detection of reproductive and developmental toxicity for human pharmaceuticals[EB/OL]. (2020-02-18)[2024-02-01]. .
8	刘昱甫. 拟胚体和斑马鱼模型评价五种食药两用物质发育毒性[D]. 南昌: 江西中医药大学, 2023. DOI: 10.27180/d.cnki.gjxzc.2023.000568 .
	LIU Y F. Embryoid bodies and zebrafish model to evaluate developmental toxicity of five kinds of drug dual-use materials[D]. Nanchang: Jiangxi University of Traditional Chinese Medicine, 2023. DOI: 10.27180/d.cnki.gjxzc.2023.000568 .
9	郑成成, 王恩力, 徐百卉, 等. 荆防颗粒浸膏对大鼠生育力与早期胚胎发育毒性研究[J]. 中国药物警戒, 2022, 19(5):505-509. DOI: 10.19803/j.1672-8629.2022.05.07 .
	ZHENG C C, WANG E L, XU B H, et al. Toxicity of the reproductive and early embraonic development of Jingfang granule extract in rats[J]. Chin J Pharmacovigil, 2022, 19(5):505-509. DOI: 10.19803/j.1672-8629.2022.05.07 .
10	WANG Y G, WU H, CHEN P, et al. Fertility and early embryonic development toxicity assessment of naringin in Sprague-Dawley rats[J]. Regul Toxicol Pharmacol, 2021, 123:104938. DOI: 10.1016/j.yrtph.2021.104938 .
11	YUE P, ZHAO X X, LU F, et al. Embryo-fetal developmental toxicity and toxicokinetics of loxoprofen tromethamine intravenously administered to pregnant rats[J]. Birth Defects Res, 2023, 115(2):240-250. DOI: 10.1002/bdr2.2116 .
12	KUWATA C, MATSUOKA T, OHSHIMA Y, et al. Effects of glucokinase activator, DS-7309, on embryo-fetal developmental toxicity in rats and rabbits[J]. Regul Toxicol Pharmacol, 2022, 129:105119. DOI: 10.1016/j.yrtph.2022.105119 .
13	RAO G K, SANTAGOSTINO S F, WONG L, et al. Repeat-dose and embryo-fetal developmental toxicity of zinpentraxin Alfa[J]. Reprod Toxicol, 2024, 123:108526. DOI: 10.1016/j.reprotox.2023.108526 .
14	BARROW P. Review of embryo-fetal developmental toxicity studies performed for pharmaceuticals approved by FDA in 2020 and 2021[J]. Reprod Toxicol, 2022, 112:100-108. DOI: 10.1016/j.reprotox.2022.06.012 .
15	LUNNEY J K, VAN GOOR A, WALKER K E, et al. Importance of the pig as a human biomedical model[J]. Sci Transl Med, 2021, 13(621): eabd5758. DOI: 10.1126/scitranslmed.abd5758 .
16	廖生钱. 小型猪在生殖毒性实验中的研究进展[J]. 畜牧兽医科技信息, 2020(9):28-29. DOI: 10.3969/J.ISSN.1671-6027.2020.09.015 .
	LIAO S Q. Research progress of miniature pigs in reproductive toxicity experiment[J]. Chin J Anim Husb Vet Med, 2020(9):28-29. DOI: 10.3969/J.ISSN.1671-6027.2020.09.015 .
17	SONG Y S, SHAO J J, SHE G B, et al. Developmental and reproductive toxicity of a recombinant protein subunit COVID-19 vaccine (ZF2001) in rats[J]. NPJ Vaccines, 2023, 8(1):74. DOI: 10.1038/s41541-023-00673-3 .
18	HOWE K, CLARK M D, TORROJA C F, et al. The zebrafish reference genome sequence and its relationship to the human genome[J]. Nature, 2013, 496(7446):498-503. DOI: 10.1038/nature12111 .
19	马雪莹. 基于斑马鱼模型研究吲唑磺菌胺的发育毒性与致毒机制[D]. 厦门: 华侨大学, 2022. DOI:10.27155/d.cnki.ghqiu.2022.000728 .
	MA X Y. Study on developmental toxicity and toxicity mechanism of indazolsulfamide based on zebrafish model[D]. Xiamen: Huaqiao University, 2022. DOI:10.27155/d.cnki.ghqiu. 2022.000728 .
20	YU J, CHENG W Q, JIA M, et al. Toxicity of perfluorooctanoic acid on zebrafish early embryonic development determined by single-cell RNA sequencing[J]. J Hazard Mater, 2022, 427:127888. DOI: 10.1016/j.jhazmat.2021.127888 .
21	张元慧, 蒋建东, 孔维佳. 非啮齿类动物在生殖毒性试验中的应用进展[J]. 中国比较医学杂志, 2019, 29(11):111-115. DOI: 10.3969/j.issn.1671-7856.2019.11.017 .
	ZHANG Y H, JIANG J D, KONG W J. Research progress with non-rodent species in reproductive toxicity studies[J]. Chin J Comp Med, 2019, 29(11):111-115. DOI: 10.3969/j.issn.1671-7856.2019.11.017 .
22	杨威, 杨明俊, 王玉柱, 等. 大气污染细颗粒物对女(雌)性生殖健康影响的研究进展[J]. 中华生殖与避孕杂志, 2019(7):602-607. DOI: 10.3760/cma.j.issn.2096-2916.2019.07.016 .
	YANG W, YANG M J, WANG Y Z, et al. Impact of atmospheric fine particles on female reproductive health[J]. Chin J Reprod Contracept, 2019(7):602-607. DOI: 10.3760/cma.j.issn.2096-2916.2019.07.016 .
23	GHAHREMANI-NASAB M, GHANBARI E, JAHANBANI Y, et al. Premature ovarian failure and tissue engineering[J]. J Cell Physiol, 2020, 235(5):4217-4226. DOI: 10.1002/jcp.29376 .
24	李虹璇, 李思慧, 冯嘉欣, 等. 卵巢早衰动物模型构建方法及比较研究进展[J]. 实验动物与比较医学, 2021, 41(6):505-514. DOI: 10.12300/j.issn.1674-5817.2021.056 .
	LI H X, LI S H, FENG J X, et al. Construction methods and comparative research progress of premature ovarian failure animal models[J]. Lab Anim Comp Med, 2021, 41(6):505-514. DOI: 10.12300/j.issn.1674-5817.2021.056 .
25	SHEN J, CAO D, SUN J L. Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure[J]. World J Stem Cells, 2020, 12(4):277-287. DOI: 10.4252/wjsc.v12.i4.277 .
26	董若曦, 朱小丹, 樊伯珍, 等. 不同剂量顺铂腹腔注射建立大鼠化疗损伤性卵巢早衰模型[J]. 实验动物与比较医学, 2020, 40(2):104-109. DOI: 10.3969/j.issn.1674-5817.2020.02.003 .
	DONG R X, ZHU X D, FAN B Z, et al. Intraperitoneal injection in different dosages of cisplatin to establish a rat model of premature ovarian failure induced by chemotherapy[J]. Lab Anim Comp Med, 2020, 40(2):104-109. DOI: 10.3969/j.issn.1674-5817.2020.02.003 .
27	HUANG Y Q, HU C, YE H F, et al. Inflamm-aging: a new mechanism affecting premature ovarian insufficiency[J]. J Immunol Res, 2019, 2019:8069898. DOI: 10.1155/2019/8069898 .
28	TAN R R, HE Y H, ZHANG S Y, et al. Effect of transcutaneous electrical acupoint stimulation on protecting against radiotherapy- induced ovarian damage in mice[J]. J Ovarian Res, 2019, 12(1):65. DOI: 10.1186/s13048-019-0541-1 .
29	孙萍, 包秀芳. 不同剂量钴⁶⁰γ射线致大鼠卵巢早衰的实验研究[J].世界最新医学信息文摘, 2017, 17(47):1. DOI:CNKI:SUN:WMIA.0.2017-47-038 .
	SUN P, BAO X F. Experimental study on premature ovarian failure induced by different doses of cobalt⁶⁰ gamma rays in rats [J]. World Latest Medical Information, 2017, 17(47):1. DOI:CNKI:SUN:WMIA.0.2017-47-038 .
30	涂晓娟. 免疫性卵巢早衰中Treg调控B细胞功能的初步研究[D]. 重庆: 中国人民解放军陆军军医大学, 2020. DOI: 10.27001/d.cnki.gtjyu.2019.000218 .
	TU X J. Autoimmune ovarian premature aging Treg regulation B cell function in the preliminary study[D]. Chongqing: The Chinese people's liberation army (PLA) army medical university, 2020. DOI: 10.27001 / , nkidc. Gtjyu. 2019.000218.
31	LI X R, XIE J X, WANG Q R, et al. MiR-21 and pellino-1 expression profiling in autoimmune premature ovarian insufficiency[J]. J Immunol Res, 2020, 2020:3582648. DOI: 10.1155/2020/3582648 .
32	潘先均, 张琪娟, 孙荣华, 等. 小鼠卵巢切除术中戊巴比妥钠麻醉使用及围手术期改良[J]. 医学信息, 2014, 27(1):45-46. DOI: 10.3969/j.issn.1006-1959.2014.01.058 .
	PAN X J, ZHANG Q J, SUN R H, et al. The use of pentobarbital sodium and improvement of ovariectomy during the perioperative period[J]. J Med Inf, 2014, 27(1):45-46. DOI: 10.3969/j.issn.1006-1959.2014.01.058 .
33	周宇, 贾玉玲, 严大为, 等. 两种小鼠卵巢早衰模型的比较[J]. 上海医学, 2018, 41(8):489-494. DOI:CNKI:SUN:SHYX.0.2018-08-012 .
	ZHOU Y, JIA Y L, YAN D W, et al. Comparison of two kinds of premature ovarian failure model in mice[J]. Shanghai Med J, 2018, 41(8):489-494. DOI:CNKI:SUN:SHYX.0.2018-08-012 .
34	VENTURELLA R, DE VIVO V, CARLEA A, et al. The genetics of non-syndromic primary ovarian insufficiency: a systematic review[J]. Int J Fertil Steril, 2019, 13(3):161-168. DOI: 10.22074/ijfs.2019.5599 .
35	EMORI C, ITO H, FUJII W, et al. Oocytes suppress FOXL2 expression in cumulus cells in mice[J]. Biol Reprod, 2020, 103(1):85-93. DOI: 10.1093/biolre/ioaa054 .
36	靳琦, 尹平, 郑慧敏. 早发性卵巢功能不全动物模型研究概述[J]. 中华中医药杂志, 2022, 37(1):305-308.
	JIN Q, YIN P, ZHENG H M. Summary of animal models of premature ovarian insufficiency[J]. Chin J Trad Chin Med Pharm, 2022, 37(1):305-308.
37	NIE X W, DAI Y J, ZHENG Y, et al. Establishment of a mouse model of premature ovarian failure using consecutive superovulation[J]. Cell Physiol Biochem, 2018, 51(5):2341-2358. DOI: 10.1159/000495895 .
38	张博航, 祁晓萱, 袁艳. 睾丸类器官在体外精子发生中的研究进展[J]. 合成生物学, 2024,5(4):770-781. DOI: 10.12211/2096-8280.2023-095 .
	ZHANG B H, QI X X, YUAN Y. Advancements in testicular organoids for in vitro spermatogenesis[J]. Synthetic Biol J, 2024,5(4):770-781. DOI: 10.12211/2096-8280.2023-095 .
39	刘丽莉, 刘昌平, 孙桃桃, 等. 锁阳水提液对环磷酰胺所致小鼠睾丸损伤的影响[J]. 淮北师范大学学报(自然科学版), 2024, 45(1):56-61. DOI: 10.3969/j.issn.2096-8248.2024.01.010 .
	LIU L L, LIU C P, SUN T T, et al. Effect of Cynomorium songaricum water extract on testicular injury induced by cyclophosphamide in mice[J]. J Huaibei Norm Univ Nat Sci, 2024, 45(1):56-61. DOI: 10.3969/j.issn.2096-8248.2024.01.010 .
40	LIN X Y, LI Q R, LI H Y, et al. Jujing Zhuyu decoction inhibits apoptosis in rats with asthenozoospermia by regulating the mitochondrial apoptosis pathway[J]. Andrologia, 2022, 54(11): e14632. DOI: 10.1111/and.14632 .
41	IRAM F, BATOOL S, SHAMEEM S, et al. Effect of aqueous garlic (Allium sativum) extract against di-(2-ethylhexyl) phthalate induced reproductive toxicity in male mice[J]. Andrologia, 2022, 54(8): e14480. DOI: 10.1111/and.14480 .
42	ZHENG X Y, GUO C M, LV Z J, et al. From animal to cell model: pyroptosis targeted-fibrosis is a novel mechanism of lead-induced testicular toxicity[J]. Food Chem Toxicol, 2023, 178:113886. DOI: 10.1016/j.fct.2023.113886 .

模型动物 Modeling animals	优点 Advantages	缺点 Disadvantages
大鼠 Rats	生物学资料全面；妊娠期短，生育力强；自发畸形率低；价格低廉，易获得	对性激素敏感，不适用于多巴胺受体激动剂和非固醇类抗炎药物的研究；对外源性蛋白的应用受限；药理活性有限或无活性
兔 Rabbits	同大鼠；且生殖道与人类最相似	对某些抗生素和消化道紊乱有易感性，其临床症状难以解释
小型猪 Minipigs	性成熟时间较其他非啮齿类动物短；器官发生期短（妊娠第11～35天）；与非人灵长类动物相比，多产，精子学资料与人类相似	胎盘缺乏转移大分子能力；妊娠期长（114 d）；受试物用量大，成本高；尚无用于研究的商业试剂盒
斑马鱼 Zebrafish	生殖周期短；每次产卵数量多；胚胎透明易观察，胎仔发育迅速；实验成本低	生殖系统基础资料相对缺乏；体外受精，与人类繁殖方式差异大

模型动物 Modeling animals	优点 Advantages	缺点 Disadvantages
大鼠 Rats	生物学资料全面；妊娠期短，生育力强；自发畸形率低；价格低廉，易获得	对性激素敏感，不适用于多巴胺受体激动剂和非固醇类抗炎药物的研究；对外源性蛋白的应用受限；药理活性有限或无活性
兔 Rabbits	同大鼠；且生殖道与人类最相似	对某些抗生素和消化道紊乱有易感性，其临床症状难以解释
小型猪 Minipigs	性成熟时间较其他非啮齿类动物短；器官发生期短（妊娠第11～35天）；与非人灵长类动物相比，多产，精子学资料与人类相似	胎盘缺乏转移大分子能力；妊娠期长（114 d）；受试物用量大，成本高；尚无用于研究的商业试剂盒
斑马鱼 Zebrafish	生殖周期短；每次产卵数量多；胚胎透明易观察，胎仔发育迅速；实验成本低	生殖系统基础资料相对缺乏；体外受精，与人类繁殖方式差异大

诱导药物 Inducing drugs	所用动物 Animals	给药方式 Administration	给药剂量和周期 Dose and time	评价指标 Evaluation indicators
环磷酰胺 Cyclophosphamide	家兔	腹腔注射	50 mg/kg连续2 d	血清FSH、E2 和AMH水平，卵巢组织病理学表现
	2～3月龄大鼠	腹腔注射	20 mg/kg，连续20 d	动情周期，血清FSH 、E2 和AMH水平，卵巢组织病理学表现
	6～8周龄C57BL/6小鼠	腹腔注射	50 mg/kg，连续14 d；100 mg/kg，连续10 d	动情周期，血清FSH 、E2 和AMH水平，卵巢组织病理学表现
顺铂 Cisplatin	Wistar大鼠	腹腔注射	4 mg/kg, 第一次注射后间隔一周再注射	动情周期，血清FSH 、E2 和AMH水平，卵巢组织病理学表现
	SD 大鼠	腹腔注射	6 mg/kg，第一次注射后间隔一周再注射
	C57BL/6小鼠	腹腔注射	50 mg/kg，连续7 d
雷公藤多苷片 Tripterygium glycosides tablet	Wistar大鼠	灌胃	50 mg/kg，连续14 d	动情周期，血清FSH 、E2 和AMH水平，卵巢组织病理学表现
	7～8周龄SD鼠		400 μg/kg，连续60 d
	8周龄SD大鼠		50 mg/kg，连续14 d
	12周龄SD大鼠		40 mg/kg，连续70 d

诱导药物 Inducing drugs	所用动物 Animals	给药方式 Administration	给药剂量和周期 Dose and time	评价指标 Evaluation indicators
环磷酰胺 Cyclophosphamide	家兔	腹腔注射	50 mg/kg连续2 d	血清FSH、E2 和AMH水平，卵巢组织病理学表现
	2～3月龄大鼠	腹腔注射	20 mg/kg，连续20 d	动情周期，血清FSH 、E2 和AMH水平，卵巢组织病理学表现
	6～8周龄C57BL/6小鼠	腹腔注射	50 mg/kg，连续14 d；100 mg/kg，连续10 d	动情周期，血清FSH 、E2 和AMH水平，卵巢组织病理学表现
顺铂 Cisplatin	Wistar大鼠	腹腔注射	4 mg/kg, 第一次注射后间隔一周再注射	动情周期，血清FSH 、E2 和AMH水平，卵巢组织病理学表现
	SD 大鼠	腹腔注射	6 mg/kg，第一次注射后间隔一周再注射
	C57BL/6小鼠	腹腔注射	50 mg/kg，连续7 d
雷公藤多苷片 Tripterygium glycosides tablet	Wistar大鼠	灌胃	50 mg/kg，连续14 d	动情周期，血清FSH 、E2 和AMH水平，卵巢组织病理学表现
	7～8周龄SD鼠		400 μg/kg，连续60 d
	8周龄SD大鼠		50 mg/kg，连续14 d
	12周龄SD大鼠		40 mg/kg，连续70 d

建模方式 Modeling methods	优点 Advantages	缺点 Disadvantages
化学药物诱导 Chemical drugs induction	造模方法简单易行，周期短，成本低，模型稳定，应用最广	卵巢功能有自然恢复的可能性，不适合进行长期的探索性研究
放射疗法诱导 Radiotherapy induction	成功率高，可重复性强，周期短，能模拟临床放疗损伤导致的卵巢早衰	不易操作，对实验者的健康会产生潜在危害；在干预过程中对其他器官也会产生损伤，影响实验结果
自身免疫 Autoimmunity	模拟程度好，适用于免疫学相关的卵巢早衰生物医学研究	造模方法复杂，成功率低，周期长
卵巢切除 Ovariectomy	模拟程度好，对动物其他组织的损伤小	永久性的卵巢功能丢失，无法应用于卵巢早衰临床治疗研究
基因敲除 Gene knockout	能明确某一特定基因对卵巢早衰的作用	成本高，对实验技术要求高，存在外源性基因表达不稳定可能
超促排卵 Superovulation	有效模拟自然衰老卵巢特征，适合卵巢衰老绝经领域研究	应用相对较少，缺少背景资料

生殖毒理学研究动物模型的建立方法及应用评价

Establishment Methods and Application Evaluation of Animal Models in Reproductive Toxicology Research

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