Srivastava R K, Gu Y, Ayloo S, Zilberstein M, Gibori G
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
J Mol Endocrinol. 1998 Dec;21(3):355-62. doi: 10.1677/jme.0.0210355.
During pregnancy, the decidua is comprised of two separate tissues located either mesometrially or antimesometrially in the uterus. Trophoblast invasion takes place only in the mesometrial decidua, where extensive angiogenesis, essential for successful implantation, occurs. Both basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been implicated in this phenomenon. The aim of this study was to determine whether the expression of both growth factors is intrinsic to decidua and occurs in the absence of conceptuses, whether their genes are expressed specifically in the mesometrial decidua, the site of angiogenesis, and whether both growth factors are developmentally and hormonally regulated. Decidual tissue was dissected from pseudopregnant rats and levels of both bFGF and VEGF mRNA were examined in mesometrial and antimesometrial decidua by semi-quantitative RT-PCR at different stages of pseudopregnancy. Although induction of decidualization triggered the mRNA expression of bFGF, VEGF mRNA expression remained unchanged. VEGF mRNA level was similar in both antimesometrial and mesometrial decidua, and remained constant throughout pseudopregnancy. In sharp contrast, bFGF mRNA was highly expressed in the mesometrial decidua at a time when extensive angiogenesis takes place in this tissue. Very little signal was observed in the antimesometrial decidua. To examine the regulation of these growth factors, we used a temperature-sensitive decidual cell line developed by transforming antimesometrial decidual cells with SV-40 tsA 209 mutant virus. These cells express both bFGF and VEGF mRNA. Because progesterone is necessary for decidualization and decidua secretes prolactin (PRL)-related hormones, we examined the role of these hormones on VEGF and bFGF mRNA expressions. Neither progesterone nor PRL had any effect on VEGF mRNA levels. However, bFGF mRNA expression was greatly stimulated by PRL. In conclusion, results of this investigation have revealed that bFGF, but not VEGF, mRNA becomes highly expressed in the mesometrial decidua, where angiogenesis occurs, and where trophoblasts, by invading decidual cells, may promote the release of bFGF. In addition, these results indicate that the locally secreted PRL-like hormone up-regulates the mRNA expression of bFGF.
在怀孕期间，蜕膜由位于子宫中膜侧或反中膜侧的两种不同组织组成。滋养层细胞侵袭仅发生在中膜侧蜕膜，在此处发生对成功着床至关重要的广泛血管生成。碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF）都与这一现象有关。本研究的目的是确定这两种生长因子的表达是否是蜕膜固有的，且在没有胚胎的情况下是否会发生，它们的基因是否在血管生成部位的中膜侧蜕膜中特异性表达，以及这两种生长因子是否受到发育和激素的调节。从假孕大鼠中分离出蜕膜组织，并在假孕的不同阶段通过半定量逆转录聚合酶链反应（RT-PCR）检测中膜侧和反中膜侧蜕膜中bFGF和VEGF mRNA的水平。尽管蜕膜化的诱导引发了bFGF的mRNA表达，但VEGF mRNA表达保持不变。反中膜侧和中膜侧蜕膜中的VEGF mRNA水平相似，并且在整个假孕期间保持恒定。形成鲜明对比的是，在该组织发生广泛血管生成时，bFGF mRNA在中膜侧蜕膜中高度表达。在反中膜侧蜕膜中观察到的信号非常少。为了研究这些生长因子的调节，我们使用了一种温度敏感的蜕膜细胞系，该细胞系是通过用SV-40 tsA 209突变病毒转化反中膜侧蜕膜细胞而建立起来的。这些细胞表达bFGF和VEGF mRNA。因为孕酮对于蜕膜化是必需的，并且蜕膜分泌催乳素（PRL）相关激素，所以我们研究了这些激素对VEGF和bFGF mRNA表达的作用。孕酮和PRL对VEGF mRNA水平均无任何影响。然而，PRL极大地刺激了bFGF mRNA的表达。总之，本研究结果表明，bFGF而非VEGF的mRNA在发生血管生成的中膜侧蜕膜中高度表达，并且滋养层细胞通过侵入蜕膜细胞可能促进bFGF的释放。此外，这些结果表明局部分泌的PRL样激素上调了bFGF的mRNA表达。
