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

哺乳动物胚胎着床的机制尚不清楚。在啮齿动物中，研究表明表皮生长因子（EGF）家族生长因子与其受体EGF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，虽然有报道称转化生长因子-α(TGF-α)作为egf家族的一员，在着床建立所必需的蜕膜中表达，但该生长因子的作用尚不清楚。本研究证实子宫腔内持续输注TGF-α刺激大鼠蜕膜生长。此外，在培养大鼠子宫内膜细胞的培养基中加入TGF-α可增加前列腺素E的分泌，前列腺素E是一种刺激个体生长的物质，且呈剂量依赖性。这些结果表明，TGF-α通过增加大鼠子宫内膜细胞中前列腺素的产生来刺激蜕膜细胞的生长。另一方面，在反刍动物中，egf家族成员和EGF-R在着床期间子宫内的表达和分布尚不清楚。本研究通过逆转录-聚合酶链反应及产物测序，研究了着床早期绵羊子宫中TGF-α mRNA和EGF-R mRNA的表达情况。TGF-α和EGF-R免疫组化染色显示，着床早期子宫内膜上皮细胞、基质细胞和滋养层细胞均呈阳性染色。TGF-α和EGF-R分别在深层腺体和滋养细胞中染色明显。这些结果提示，TGF-α在子宫内膜和滋养细胞中的表达可能对这些组织发挥局部作用，从而促进绵羊胚胎植入成功。

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.