重复药物流产小鼠模型后续妊娠结局及早期妊娠相关分子机制研究

发布时间：2018-04-11 14:57

本文选题：药物重复流产 + RU486　；参考：《北京协和医学院》2013年硕士论文

【摘要】：药物流产是指口服药物达到终止早孕的方法,由于此程序简单,创伤性小,实用性较强等优点使得越来越多的妇女选择这种方法终止早期妊娠。近年来,在我国选择药物流产的未经产妇女、未婚妇女和女性青少年的比例相对较高,其中多次药物流产的在人工流产中也占有一定比例,使得药物流产(尤其是多次药物流产)后再次妊娠结局成为目前人们普遍关注的问题。因此我们建立了药物重复流产小鼠模型,对经历两次药物流产后小鼠再次妊娠结局和其早孕时期相关分子机制进行了一些探索。目的：研究重复药物流产小鼠后续妊娠过程中的妊娠率、仔鼠存活率和体重的影响及早期妊娠过程中相关分子机制。方法：利用BALB/c小鼠腹腔注射2mg/kg RU486建立重复药物流产小鼠模型,记录后续生产仔鼠出生时间和体重,并采用免疫组化和实时定量PCR检测了早孕期间相关分子表达变化。结果：在连续观察的18个交配周期中,实验组和对照组累积妊娠率(受孕率)基本一致,药物流产对总体生育力无影响。但在前10个周期内,实验组生育力与对照组相比表现出延迟／降低(p0.05)。随着胎次的增加实验组胎产仔数明显下降(p0.05)。在对照组1-3胎次中哺乳成活率具有逐渐增加的趋势；而在实验组1-3胎次中具有明显降低的趋势(直线回归,F=1680.33,p0.05)。随着胎次的增加,在哺乳过程中,实验组雄性小鼠死亡所占比例明显增高(51.9%-86.2%)。两组幼鼠体质量比较,雌性仔鼠在对照组与实验组间无明显差异(p0.05)；实验组雄性仔鼠体质量低于对照组,尤其是第2胎和第3胎明显降低(t’=1.6851和t,=1.9231,均p0.05)。妊娠早期相关基因表达检测的实时定量PCR结果显示,妊娠D7.5, SGK1、GR在实验组的表达均低于对照组,具有明显的统计学差异(p0.05)。P53在实验组的表达高于对照组,具有显著性统计学差异(p0.01)。结论：两次药物流产小鼠的后续妊娠过程中,生育力延迟／降低,随着胎次的增加产仔率和哺乳成活率明显下降,并且雄性仔鼠的死亡率明显升高。在妊娠D7.5, SGK1、GR表达低于对照组,与早期流产的有关。
[Abstract]:Drug abortion is a method of terminating early pregnancy with oral medicine. Because of the advantages of simple procedure, small trauma and strong practicability, more and more women choose this method to terminate early pregnancy.In recent years, the proportion of unmarried women and female adolescents who choose drug abortion in our country is relatively high, among which many drug abortions also account for a certain proportion in induced abortion.Drug abortion (especially multiple drug abortion) has become a common concern at present.Therefore, we established a mouse model of drug repeated abortion, and explored the related molecular mechanism of the second pregnancy outcome and its early pregnancy in mice after two drug abortions.Aim: to study the effects of repeated drug abortion on the pregnancy rate, the survival rate and body weight of newborn mice and the related molecular mechanisms during early pregnancy.Methods: the mouse model of repeated drug abortion was established by intraperitoneal injection of 2mg/kg RU486 into BALB/c mice. The birth time and body weight of the mice were recorded. The expression of related molecules during early pregnancy was detected by immunohistochemistry and real-time quantitative PCR.Results: in 18 consecutive mating cycles, the cumulative pregnancy rate (pregnancy rate) of the experimental group and the control group were basically the same, and the drug abortion had no effect on the overall fertility.But in the first 10 cycles, the fertility of the experimental group was delayed / decreased by 0.05% compared with the control group.With the increase of the number of births, the litter size of the experimental group decreased significantly (p 0.05).The survival rate of breast-feeding increased gradually in the control group (1-3 births), but decreased significantly in the experimental group (linear regression analysis: F = 1680.3p0.05).With the increase of the number of births, the proportion of male mice dying in the experimental group increased significantly during lactation, 51.9% -86.2%.There was no significant difference in body mass between the control group and the experimental group, and the body weight of the male offspring in the experimental group was lower than that in the control group, especially in the second and third embryos. The body weight of the female offspring was significantly lower than that of the control group, especially the second and third embryos, with a significant decrease of 1.6851 and 1.9231, respectively (p0.05).The results of real-time quantitative PCR showed that the expression of D7.5 and SGK1GR in the experimental group was lower than that in the control group, and the expression of p0.05. p53 in the experimental group was significantly higher than that in the control group (p0.01).Conclusion: during the subsequent pregnancy of mice induced by two times of drug abortion, fertility was delayed / decreased, and the birth rate and the survival rate of lactation decreased with the increase of birth order, and the mortality rate of male mice increased obviously.The expression of gr in gestational D 7.5 was lower than that in control group, which was related to early abortion.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R-332;R719.31

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