Das S K, Chakraborty I, Wang J, Dey S K, Hoffman L H
Department of Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66103, USA.
Biol Reprod. 1997 Jun;56(6):1390-9. doi: 10.1095/biolreprod56.6.1390.
The endometrial vasculature undergoes expansion during preimplantation stages and, even more prominently, after implantation. In addition to angiogenesis, vascular hyperpermeability accompanies the attachment and invasion of blastocysts into the uterine lining. Vascular endothelial growth factor (VEGF) is an angiogenic factor expressed in mammalian uteri that also has potent activity in inducing vascular permeability. Rabbit uteri were examined using Northern and in situ hybridization to assess the temporal and spatial expression of VEGF and its receptor (Flk-1, Flt-1) mRNAs during the pre- and peri-implantation periods (Days 0-8). Steady-state levels of VEGF mRNA were highest in endometrium at estrous and peri-implantation stages (Days 6-8). In situ hybridization revealed a shift from uniform expression of VEGF transcripts throughout the uterus at estrus and Day 4, to an endometrial epithelial localization just before and during implantation. At implantation sites, a pronounced signal was present in the trophoblastic knobs, the syncytial aggregates that attach to and invade the endometrium. VEGF protein was detected by immunoblot analysis in peri-implantation-stage uteri but was below the limit of detection in estrous endometrium. VEGF receptor mRNAs were expressed in the uterus at all stages examined, with high levels of Flk-1 and Flt-1 at estrus and again just before implantation, 6-3/4 days pregnant. The high level just before implantation correlates with in situ hybridization results showing a prominent, but transient, signal for Flk-1 mRNA in the endometrial epithelium. During implantation, Flk-1 mRNA was associated with blood vessels of the endometrial stroma. We conclude that VEGF is a candidate factor for the induction of vascular hyperpermeability at implantation in the rabbit and in the angiogenic process that follows.
在植入前阶段，子宫内膜血管系统会发生扩张，而在植入后，这种扩张更为显著。除了血管生成外，血管高通透性还伴随着囊胚附着和侵入子宫内膜的过程。血管内皮生长因子（VEGF）是一种在哺乳动物子宫中表达的血管生成因子，它在诱导血管通透性方面也具有强大的活性。利用Northern杂交和原位杂交技术对兔子宫进行检测，以评估植入前和植入期（第0 - 8天）VEGF及其受体（Flk - 1、Flt - 1）mRNA的时空表达。VEGF mRNA的稳态水平在发情期和植入期（第6 - 8天）的子宫内膜中最高。原位杂交显示，在发情期和第4天，VEGF转录本在整个子宫中均匀表达，而在植入前和植入期间则转变为子宫内膜上皮定位。在植入部位，滋养层结节（即附着并侵入子宫内膜的合体细胞聚集体）中存在明显的信号。通过免疫印迹分析在植入期子宫中检测到了VEGF蛋白，但在发情期子宫内膜中低于检测限。在所检测的所有阶段，子宫中均表达VEGF受体mRNA，在发情期以及怀孕6 - 3/4天植入前，Flk - 1和Flt - 1水平较高。植入前的高水平与原位杂交结果相关，该结果显示子宫内膜上皮中Flk - 1 mRNA有一个显著但短暂的信号。在植入过程中，Flk - 1 mRNA与子宫内膜基质的血管相关。我们得出结论，VEGF是兔植入时诱导血管高通透性以及随后血管生成过程的候选因子。
