关键词: 不明原因复发性流产, 流产小鼠模型, CBA/J, DBA/2, 动情周期, 合笼, 阴栓

Abstract: Unexplained recurrent spontaneous abortion (URSA) is a complex and challenging pregnancy disorder with unclear pathogenesis. The CBA/J × DBA/2 (Clark) mouse model is a well-recognized classic model for URSA, characterized by recessive, recurrent, and peri-implantation embryo resorption with a stable abortion rate of 20%-30%. This inbred model features a uniform genetic background, and the abortion rate attributed to chromosomal abnormalities is approximately 4%, consistent with human etiological data. However, challenges remain in model establishment, including variable pregnancy rates, inaccurate pregnancy timing determination, and high modeling costs. This study systematically summarizes the key technical points and practical experience for constructing the Clark model. To improve pregnancy rate, we optimized animal selection, age matching, housing environment, estrous cycle identification, and male-female pre-exposure, and clarified that superovulation is unsuitable for this model, while male sexual refractory period and Bruce effect should be avoided. We also established a multi-dimensional pregnancy judgment system combining vaginal plug inspection, dynamic body weight monitoring, fecal observation, abdominal palpation, visual inspection, and laparotomy. Novel findings include: a slight body weight decrease of 1%-5% on the day after plug detection; a body weight gain of approximately 1.0 g at GD4-6 (peri-implantation) indicating early pregnancy; a body weight gain ≥2.0 g at GD8 allowing earlier pregnancy confirmation; and drier feces in pregnant mice at GD4-6. This paper systematically organizes the key techniques in the whole process of model construction, which can significantly improve pregnancy rate and gestational age accuracy, reduce modeling costs, and provide a stable and reproducible model basis for URSA pathogenesis research and drug efficacy evaluation.

Key words: unexplained recurrent spontaneous abortion, abortion mouse model, CBA/J, DBA/2, estrous cycle, caged together, vaginal plug