【作者】 刘新；

【导师】 王自能；

【作者基本信息】 暨南大学 ， 妇产科学， 2005， 硕士

【摘要】 目的 观察米非司酮对小鼠成熟卵泡、囊胚发育及超微结构的影响,探讨小剂量米非司酮紧急避孕的机理。 方法 1.雌性昆明小鼠40只,随机均分为4组:对照组（A₁组）,米非司酮剂量0.048mg组（B₁组）,0.143mg组（C₁组）和0.429mg组（D₁组）。4组动物均在动情前期以灌胃方式给药,10h后取其双侧卵巢用透射电镜观察成熟卵泡超微结构的改变。 2.雌性昆明小鼠60只,随机均分为4组:对照组（A₂组）,米非司酮剂量0.048mg组（B₂组）,0.143mg组（C₂组）和0.429mg组（D₂组）。4组动物均按常规超排卵后合笼,在注射hCG后108～110h取囊胚在光学显微镜下观察生长发育的情况,并用透射电镜观察4组囊胚超微结构的变化。 结果 1.米非司酮对小鼠成熟卵泡超微结构的影响 1.1 米非司酮对小鼠成熟卵泡中卵丘颗粒细胞超微结构的影响 与A₁组相比,B₁组小鼠卵丘颗粒细胞外形无明显改变,细胞的间隙变宽,部分线粒体水肿明显。C₁组小鼠卵丘颗粒细胞外形不规则,细胞间隙宽,可见髓样小体,线粒体更加肿胀,呈空泡状,嵴断裂、消失,核糖体脱落,细胞核变化不明显。D₁组小鼠颗粒细胞中有凋亡现象出现,胞浆内可见部分凋亡小体,线粒体大部分空泡化,内质网明显肿胀,细胞核形态不规则。 1.2 米非司酮对小鼠成熟卵泡中卵泡内膜细胞超微结构的影响 与A₁组相比,B₁组小鼠卵泡内膜细胞胞浆内脂滴的电子致密度明显降低,更多还原

【Abstract】 ObjectiveTo observe effects of mifepristone （MP） on the development and ultrastructure of mouse mature follicle and blastocysts in vivo and to investigate the action mechanism of mifepristone used for emergency contraception.Materials and Methods1. 40 female mice were equally divided into 4 groups: control group （group A₁）, 0.048mg MP group （group B₁）, 0.143mg MP group （group C₁）, and 0.429mg MP group （group D₁）. The female mice of 4 groups were given MP by the pouring stomach method in the proestrus, and ultrastructural changes of mature follicle were observed by transmission electron microscope 10 h later.2. 60 female mice were equally divided into 4 groups: control group （group A₂）, 0.048mg MP group （group B₂）, 0.143mg MP group （group C₂）, and 0.429mg MP group （group D₂）. The female mice of 4 groups were undergone a routine superovulation method and then matched. The development of obtained blastocysts was evaluated, and ultrastructural changes of the blastocysts were observed by transmission electron microscope.Results1. Influence of MP on the ultrastructure of mouse mature follicles1.1 Influence of MP on the ultrastructure of cumulus granulosa cells.In comparison with group Ai, shape of cumulus granulosa cells showed no difference in group Bi, there were gaps between cells, some mitochondria and endoplasmic reticulum were distinctly edematous. In group Ci, granulosa cells were irregular in shape, the cellular contact was loosened, myelin figures were found in the cytoplasm and mitochondria were frequently vacuolated, there was no obvious change on nucleolus. In group Di, apoptosis often appeared, some apoptotic bodies were found in the cytoplasm , most mitochondria were frequently vacuolated, endoplasmic reticulum was distinctly edematous. The nucleoli were irregular in shape .1.2 Influence of MP on the ultrastructure of mouse theca cells in mature folliclesIn comparison with group Ai , electron density of the lipid droplets was decreased in group B^ some mitochondria were edematous and myelin figures were found in the cytoplasm. In group Ci, the cells were narrow and elongated, most mitochondria were vacuolated, endoplasmic reticulum was distinctly edematous , the number of lipid droplets decreased obviously. In group Di, the cells were more narrow and elongated than before, lipid droplet disappeared, lipofuscin were found in the cytoplasm, the number of mitochondria decreased obviously, the ratio of nucleolus to cytoplasm decreased.1.3 Influence of MP on the ultrastructure of oocyte in mature follicles.In group Ai, ultrastructure of oocyte appeared normal morphology. A lot of minute microvilli stretching into zona pellucida was observed, and abundant mitochondria and ribosomes were encountered in cytoplasma. In comparison with group Ai , some mitochondria were vacuolated in group Bi. In group Ci, a lot of filamentous crystals were found and mitochondria were vacuolated. In group Di, filamentous crystals were more numerous than before, endoplasmic reticulum was edematous and mitochondria were vacuolated.2. Influence of mifepristone on the development of blastocystIn comparison with group A2, the developmental rate of blastocysts in group B2 showed no difference （P>0.05）, while the developmental rate of blastocysts in both group C2 and group D2 was significantly lower （P<0.05）. With doses of 0.143mg and0.429mg（C2> D2 group）, the blastocysts showed granular appearance of the cytoplasm, irregular cell borders, enlarged perivitelline space and degeneration. 3. Influence of MP on the ultrastructural changes of blastocystUltrastructure of the blastocysts in group B2 was similar to group A2, except a little number of lipid droplets in the cytoplasm. In group C2, the microvilli on apical surface was decreased in number or even disappeared, mitochondria were under developed, a lot of filamentous crystals were found in the cytoplasm. Cellular junctions were defected. In group D2, the blastocyst cells were irregular in shape, mitochondria were frequently vacuolated, the nucleolus was enlarged, nuclear membrane was ruptured, and chromatin was loosened.Conclusion1. MP could damage to the ultrastructure of mouse cumulus granulose cell in mature follicle and make lipid droplet decreased in the theca cells, restrain ovulation and damage to the ultrastructure of mouse ovulated oocyte in mature follicle.2. MP could damage to the ultrastructure of mouse blastocyst, and was responsible for the inhibition of blastocyst development. The inhibitory effect of MP would be in a dose -dependent.更多还原