Expression and physiological role of growth factor in uterus during implantation.

在哺乳动物体内植入的机制仍然难以捉摸。在啮齿类动物中，表皮生长因子(EGF)家族的生长因子家族与其受体EGF-R结合，并通过子宫和胚胎细胞的增殖和分化在着床过程中发挥重要作用。在大鼠中，转化生长因子-α(转化生长因子-α)是一种强有力的表皮生长因子家族成员，虽然有报道在蜕膜中表达，这对着床的建立是必不可少的，但该生长因子的作用尚不清楚。本研究证实子宫腔内持续注入转化生长因子-α可促进大鼠蜕膜生长。此外，在培养的大鼠子宫内膜细胞中，向培养液中加入转化生长因子-α可剂量依赖性地增加蜕膜生长刺激物前列腺素E的分泌。这些结果表明，转化生长因子-α通过增加子宫内膜细胞中前列腺素的产生来刺激蜕膜生长。另一方面，在反刍动物中，胚胎生长因子家族成员和表皮生长因子受体在子宫中的表达和分布尚不清楚。本研究通过逆转录-聚合酶链式反应和产物测序，显示了转化生长因子-EGF-α和EGF-RmRNA在绵羊着床早期子宫中的表达。免疫组织化学染色显示，植入早期子宫内膜上皮细胞、间质细胞和滋养层细胞均呈阳性染色。α和EGF-R免疫组织化学染色显示，子宫内膜上皮细胞、基质细胞和滋养层细胞均呈阳性染色。此外，深部腺体和滋养层细胞表达明显的转化生长因子-α，提示转化生长因子-α在子宫内膜和滋养层细胞中的表达可能是局部作用于这些组织，从而促进绵羊着床成功。

The mechanism of implantation in the mammalia is still elusive. In the rodent, it is suggested that the epidermal growth factor (EGF) family of growth factors binds to its receptor, EGF receptor (EGF-R), and plays important roles in the implantation process through proliferation and differentiation of uterine and embryonic cells. In the rat, although transforming growth factor-α(TGF-α), a potent EGF-family member, is reported to be expressed in the decidua which is essential for the establishment of implantation, roles of this growth factor are not clarified. In this study, it was proved that continuos intraluminal infusion of TGF-α into the uterine lumen stimulates decidual growth in the rats. Further, in the culture of rat uterine endometrial cells addition of TGF-α into the medium increased the secretion of prostaglandin E, a stimulator of decidual growth, dose-dependently. These results suggest that TGF-α stimulates decidual growth by increasing the production of prostaglandins in the rat endometrial cells.On the other hand, in the ruminant, expression and distribution of EGF-family members and EGF-R in the uterus during implantation remain to be elucidated. This study showed expressions of TGF-α mRNA and EGF-R mRNA in the ovine uterus during the early implantation period by reverse transcription-polymerase chain reaction and sequencing of the products. Furthermore, immunohistochemical stainings of TGF-α and EGF-R revealed that the epithelial and stromal cells of the endometrium and the trophoblastic cells were all positive stained during the early implantation period. In addition, distinct staining was evident in the deep gland for TGF-α and in the trophoblastic cells for EGF-R.These results suggest that TGF-α expressed in the endometrium and trophoblast may exert its effects locally on these tissues to progress successful implantation in the sheep.