金色中仓鼠胚胎植入小鼠子宫后PTEN、FAK、Shc信号分子的异常表达

摘要

Interspecific embryos always abort at certain phase in pregnancy. The majority of previous studies focused on descriptions of macrostructure and anatomic differences and molecular mechanisms of these phenomena were rarely studied. In order to elucidate the possible roles of signal molecules in failure of interfamily pregnancy, we compared the expressive differences of integrin alpha v beta 3, FAK, p-ERK, IGFⅡ, IGFBP-1, Shc, PTEN and MMP-2, -9 between interfamily and intraspecific fetuses by immunohistochemistry and gelatin zymography. Interfamily pregnancy was achieved by transferring embryos of golden hamster Mesocricetus auratus into pseudopregnant mouse Mus musculus uteri. Interfamily pregnant fetuses of day 4, 8 and 12 formed the experimental group. The intraspecific pregnant mice uteri after implantation of mice embryos to the uteri of pseudopregnant mice at corresponding time provided positive and negative controls, respectively. The immunohistochemical results showed that the expressions of integrin αvβ3, IGF-Ⅱ, IGFBP-1, PTEN, Shc and FAK of interfamily fetuses on day 8 were all different to those of normal intraspecific pregnancy day 8. While the expressive localization and intensity of p-ERK both had no evidently different between interfamily and interspecific pregnancy on day 8. Gelatin zymography indicated obvious differences of secretive modes of MMP-2 and -9 between interfamily and intraspecific pregnancy. The results suggested that these signal molecules differentially expressed in uteri participate to the formation of abnormal histological exhibitions in maternal-fetal interface of interfamily pregnancy.%除了马属动物外,种间妊娠的胚胎总在妊娠的一定时期流产.以往的研究多集中在宏观结构和解剖学差别的研究上,对于这种现象产生的分子机制却少有报道.为了从信号分子角度阐明种间妊娠维持失败的可能原因,我们通过免疫组化和明胶酶谱法比较了科间和同种妊娠部位整合素αvβ3、FAK、p-ERK、IGFⅡ、IGFBP-1、Shc、PTEN和MMP-2、-9表达的差异.科间妊娠是将金色中仓鼠(Mesocricetus auratus)的胚胎移植入假孕小鼠(Mus musculus)子宫并取妊娠D4、D8、D12的子宫为实验材料,相应时间同种小鼠胚胎移植小鼠妊娠后的子宫和假孕小鼠子宫分别为阳性和阴性对照.免疫组化结果表明: D8时,科间妊娠孕体integrin αvβ3、IGF-Ⅱ、IGFBP-1、PTEN、Shc、FAK的表达强度均与正常同种妊娠有差异.而妊娠D8时同种、科间妊娠子宫p-ERK的表达部位与表达量无明显差异.明胶酶谱显示,科间妊娠时MMP-2,-9的分泌模式与同种妊娠明显不同.这些结果表明,上述信号通路分子的差异表达有可能是造成科间妊娠时母胎界面异常的组织学表现的一个原因.