Characteristics Evaluation and Application Analysis on Animal Models of Recurrent Spontaneous Abortion

doi:10.12300/j.issn.1674-5817.2024.013

Abstract

Abstract:

Objective To summarize and evaluate the characteristics of current recurrent spontaneous abortion (RSA) animal models at home and abroad, and to provide reference and guidance for the standardized preparation of RSA models. Methods "Recurrent spontaneous abortion" and "animal model" were used as co-keywords in CNKI, Wanfang, VIP, PubMed and Web of Science databases to search the RSA animal experimental literature, covering the period up to January 20, 2024, and a total of 1 411 articles were collected. The analysis focused on construction methods and essential elements of RSA animal models, the modeling process and result evaluation, as well as the application of these models in pharmacological and pharmacodynamic research. An Excel table was established for systematic analysis and discussion. Results A total of 138 experimental studies were obtained after screening. In constructing RSA animal models, immunological models were the most widely used in Western medicine (96.92%), with the Clark model being the main one (92.31%). In traditional Chinese medicine (TCM) models, 70.00% were kidney deficiency-luteal inhibition-syndrome combination models, 20.00% were kidney deficiency and blood stasis models, and 10.00% were deficiency-heat syndrome models. Most animals were selected at 6-8 weeks (33.86%) and 8 weeks (32.28%) of age. The majority of animals were paired for mating at 18:00 on the day of cage pairing. In 81.03% of literatures, vaginal plugs were checked once the following morning, with 8:00 being the most common time (17.02%). The most commonly used drug administration cycle was 14 days of continuous gavage after pregnancy. Among the tested drugs, Western drugs were mainly protein-based (29.17%), while TCM drugs were mainly TCM decoction (81.11%). The most frequently used methods for detecting indicators included visual observation of embryos (22.54%), western blot (15.96%), PCR (13.58%), ELISA (12.91%), HE staining (10.80%) and immunohistochemistry (9.39%). Conclusion The etiology of RSA is complex, and corresponding animal models should be established based on different etiologies. Clark model is commonly used in the construction of Western medicine model, while the kidney deficiency-luteal inhibition-syndrome combination model is predominant in TCM. RSA animal model is widely used in related research, but systematic evaluation needs to be strengthened.

Key words: Recurrent spontaneous abortion, Animal model, Model characteristics, Model evaluation

CLC Number:

R714.21

DING Tiansong,XIE Jinghong,YANG Bin,et al. Characteristics Evaluation and Application Analysis on Animal Models of Recurrent Spontaneous Abortion[J]. Laboratory Animal and Comparative Medicine, 2024, 44(4): 393-404. DOI: 10.12300/j.issn.1674-5817.2024.013.

Figures/Tables 7

References 43

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模型分类 Model classifications	动物品种品系 animal strains	文献频数（百分比/%） Frequency (Percentage /%)	造模方法 Modeling methods
西医模型 Western medicine model	CBA/J小鼠（♀）×DBA/2小鼠（♂）	120 （92.31）	无需药物干预，成功妊娠即成模
	BALB/c小鼠（♀）×BALB/c小鼠（♂）	4 （3.08）	子宫或腹腔注射β2-GP1
	Swiss白化小鼠（♀）×Swiss白化小鼠（♂）	2 （1.54）	腹腔注射LPS
	SD大鼠（♀）×SD大鼠（♂）	1 （0.77）	皮下注射溴隐亭
	C57BL/6小鼠（♀）×C57BL/6小鼠（♂）	1 （0.77）	腹腔注射LPS
	CBA/J小鼠（♀）×CBA/J小鼠（♂）	1 （0.77）	尾静脉注射JL-1
	SD大鼠（♀）×SD大鼠（♂）	1 （0.77）	皮下注射aCL-IgG
中医病证结合模型 TCM disease and syndrome combination model	SD大鼠（♀）×SD大鼠（♂）	7 （70.00）	羟基脲灌胃+米非司酮灌胃（肾虚-黄体抑制）
	CBA/J小鼠（♀）×BALB/c小鼠（♂）	2 （20.00）	羟基脲灌胃+肾上腺素皮下注射（肾虚血瘀）
	CBA/J小鼠（♀）×DBA/2小鼠（♂）	1 （10.00）	附子、干姜、肉桂溶液灌胃（虚热）

模型分类 Model classifications	动物品种品系 animal strains	文献频数（百分比/%） Frequency (Percentage /%)	造模方法 Modeling methods
西医模型 Western medicine model	CBA/J小鼠（♀）×DBA/2小鼠（♂）	120 （92.31）	无需药物干预，成功妊娠即成模
	BALB/c小鼠（♀）×BALB/c小鼠（♂）	4 （3.08）	子宫或腹腔注射β2-GP1
	Swiss白化小鼠（♀）×Swiss白化小鼠（♂）	2 （1.54）	腹腔注射LPS
	SD大鼠（♀）×SD大鼠（♂）	1 （0.77）	皮下注射溴隐亭
	C57BL/6小鼠（♀）×C57BL/6小鼠（♂）	1 （0.77）	腹腔注射LPS
	CBA/J小鼠（♀）×CBA/J小鼠（♂）	1 （0.77）	尾静脉注射JL-1
	SD大鼠（♀）×SD大鼠（♂）	1 （0.77）	皮下注射aCL-IgG
中医病证结合模型 TCM disease and syndrome combination model	SD大鼠（♀）×SD大鼠（♂）	7 （70.00）	羟基脲灌胃+米非司酮灌胃（肾虚-黄体抑制）
	CBA/J小鼠（♀）×BALB/c小鼠（♂）	2 （20.00）	羟基脲灌胃+肾上腺素皮下注射（肾虚血瘀）
	CBA/J小鼠（♀）×DBA/2小鼠（♂）	1 （10.00）	附子、干姜、肉桂溶液灌胃（虚热）

年龄 Age	文献频数/次（小鼠/大鼠） Frequency/times (mouse/rat)	百分比/%（小鼠/大鼠） Percentage /% (mouse/rat)
6～8周龄 6～8 weeks old	43 （40/3）	33.86 （31.50/2.26）
8周龄 8 weeks old	41 （40/1）	32.28 （31.50/0.79）
8～10周龄 8～10 weeks old	28 （27/1）	22.05 （21.26/0.79）
≥10周龄 ≥10 weeks old	8 （7/1）	6.30 （5.51/0.79）
10～12周龄 10～12 weeks old	3 （2/1）	2.26 （1.57/0.79）
8～12周龄 8～12 weeks old	3 （3/0）	2.26 （2.26/0）
9～11周龄 9～11 weeks old	1 （1/0）	0.79 （0.79/0）

年龄 Age	文献频数/次（小鼠/大鼠） Frequency/times (mouse/rat)	百分比/%（小鼠/大鼠） Percentage /% (mouse/rat)
6～8周龄 6～8 weeks old	43 （40/3）	33.86 （31.50/2.26）
8周龄 8 weeks old	41 （40/1）	32.28 （31.50/0.79）
8～10周龄 8～10 weeks old	28 （27/1）	22.05 （21.26/0.79）
≥10周龄 ≥10 weeks old	8 （7/1）	6.30 （5.51/0.79）
10～12周龄 10～12 weeks old	3 （2/1）	2.26 （1.57/0.79）
8～12周龄 8～12 weeks old	3 （3/0）	2.26 （2.26/0）
9～11周龄 9～11 weeks old	1 （1/0）	0.79 （0.79/0）

造模过程评定项目 Molding process assessment item	时间或次数 Time or frequency	文献频数（小鼠/大鼠） Frequency (mouse/rat)	百分比/%（小鼠/大鼠） Percentage /% (mouse/rat)
合笼交配时间 Cage mating	交配日18:00	6 （6/0）	60.00 （60.00/0）
	交配日20:00	2 （2/0）	20.00 （20.00/0）
	交配日17:00	1 （1/0）	10.00 （10.00/0）
	交配日晚上	1 （1/0）	20.00 （20.00/0）
阴栓检查频次 Frequency vaginal plug examination	合笼后每日1次	47 （42/5）	81.03 （72.41/8.62）
阴栓检查频次 Frequency vaginal plug examination	合笼后每日2次	11 （8/3）	18.97 （13.79/5.17）
阴栓检查时间 Vaginal plug examination time	次日清晨	13 （11/2）	27.66 （23.40/4.26）
	次晨	8 （8/0）	17.02 （17.02/0）
	次日8:00	8 （8/0）	17.02 （17.02/0）
	次日早晨	7 （5/2）	14.89 （10.64/4.26）
	仅提及每日1次	2 （2/0）	4.26 （4.26/0）
	次日5:00-6:00	1 （1/0）	2.13 （2.13/0）
	次日6:00	1 （1/0）	2.13 （2.13/0）
	次日6:00-7:00	1 （1/0）	2.13 （2.13/0）
	次日7:00	1 （1/0）	2.13 （2.13/0）
	次日8:30	1 （1/0）	2.13 （2.13/0）
	次日10:00	1 （1/0）	2.13 （2.13/0）
	次日9:00-11:00	1 （1/0）	2.13 （2.13/0）
	次日早晨	1 （1/0）	2.13 （2.13/0）
	次日上午	1 （0/1）	2.13 （2.13/0）
	次日8:00和14:00	5 （1/0）	45.45 （45.45/0）
	次日8:00和15:00	1 （1/0）	9.09 （9.09/0）
	次日早晚7:00	1 （1/0）	9.09 （9.09/0）
	次日早晚8:00	1 （1/0）	9.09 （9.09/0）
	次日早晚9:00	1 （1/0）	9.09 （9.09/0）
	次日早、晚	1 （1/0）	9.09 （9.09/0）
	仅提及每日2次	1 （1/0）	9.09 （9.09/0）