Establishment and Evaluation of Spontaneous Abortion Mouse Models of Progesterone Insufficiency Induced by Mifepristone

doi:10.3969/j.issn.1674-5817.2016.05.001

Abstract

Abstract: Objective To establish spontaneous abortion mouse models of progesterone insufficiency induced by mifepristone (RU486) to provide an ideal animal model for the mechanism of spontaneous abortion and clinical practice of supplying progesterone in pregnancy period. Methods Adult female mice were randomly divided into a RU486 high-dose group (50 μg/100 μL propylene glycol/only), middle-dose group (25 μg/100 μL propylene glycol/only), low-dose group (10 μg/100 μL propylene glycol/only) and solvent control group (100 μL propylene glycol/only). A subcutaneous injection of RU486 or solvent was given on pregnancy day 8, and the phenotype of pregnant mice and neonatal mice were observed on pregnancy day 10(d10) and after their delivery. The peripheral blood and uterus tissues of the mice in each group were collected on d10 to detect the levels of their serum estradiol (E₂) and progesterone(P₄). The uterine tissue differentially expressed genes between the experimental and control groups were screened and analyzed by Gene Chip Technology, and three of them were validated by Western blot. Results The abortion proportions were 100%, 46.0% and 13.9% respectively in the high-dose group, middle-dose group and low-dose group, and some embryos stopped developing and were absorbed in the uterus were observed in the middle-dose group, whereas the newborn mouse birth weights in the low-dose group were significantly lower than those in the control group (P<0.05). Compared with those of the control group, the E₂ levels of the pregnant mice serum of the middle-dose group were increased (P<0.05) and P₄ levels were decreased (P<0.001), while the E₂ levels of the pregnant mice serum of the low-dose group were decreased (P<0.05), and P₄ levels were increased (P<0.05). The Gene Chip and Western blot analysis and verification discovered that the expression of CDK4 in the uterine tissues was significantly reduced in the middle-dose group (P<0.05) compared with the control group, the expression of Bax was also significantly decreased (P<0.05), whereas the expression of CCND2 significantly increased and was statistically significant (P<0.05). Conclusion The appropriate dose of RU486 able to induce the pregnancy loss of pregnant mice after embryo implantation or neonatal weight loss. It might become a new animal model to be used for study of pathological mechanisms of the abortion or intrauterine growth restriction induced by progesterone deficiency in women pregnancy period.

Key words: Mifepristone(RU486), Spontaneous abortion, IUGR, CDK4, Bax

CLC Number:

R714.21Q95-33

YANG Qian, YU Lin, GU Yan, SHI Yan, HE Ya-ping, WANG Jian. Establishment and Evaluation of Spontaneous Abortion Mouse Models of Progesterone Insufficiency Induced by Mifepristone[J]. Laboratory Animal and Comparative Medicine, 2016, 36(5): 327-333.

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