Winther H, Ahmed A, Dantzer V
Institute of Anatomy and Physiology, Department of Anatomy, The Royal Veterinary and Agricultural University, Copenhagen, Denmark.
Placenta. 1999 Jan;20(1):35-43. doi: 10.1053/plac.1998.0350.
Placental angiogenesis and growth are crucial elements in embryonic and later fetal development. Vascular endothelial growth factor (VEGF) and its specific receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) compose potent ligand receptor systems involved in angiogenesis and microvascular hyperpermeability. In the present immunohistochemical study, VEGF, Flt-1 and KDR were localized in uterus of cyclic non-pregnant pigs and in the porcine epitheliochorial placenta throughout gestation. Emphasis was placed on early gestational stages, where morphological studies have demonstrated extensive angiogenesis during initial placentation. The results revealed a high correlation in spatiotemporal distribution between the ligand and its receptors and a surprising demonstration of VEGF receptors in several non-endothelial cells. In non-pregnant pigs, VEGF, Flt-1 and KDR exhibited moderate to intense staining in uterine luminal epithelium and smooth muscle cells of the vessel walls. Endothelial cells of arteries and arterioles revealed labelling for Flt-1 and KDR, whereas the uterine glandular epithelium displayed intense KDR immunoreactivity at the late luteal phase. During gestation the uterine luminal epithelium demonstrated weak ligand and receptor immunostaining in the first half of early gestation [< or = 21 days post coitus (p.c.)], whereas later stages (> or = 21 days p.c.) displayed intense immunolabelling. Endothelial cells, smooth muscle cells of the vessel walls and uterine glandular epithelium revealed intense ligand and receptor immunoreactivity throughout gestation. In the fetal part of the placenta, VEGF, Flt-1 and KDR immunostaining displayed moderate to intense reactivity in the trophoblast throughout gestation, except during the second half of early gestation (days 21-30 p.c.). Fetal vessel walls were also immunopositive for VEGF, Flt-1 and KDR. Taken together, the results imply that the VEGF, Flt-1 and KDR ligand receptor system participate in the regulations of porcine placentation and that it in addition to its angiogenic properties also may influence the cellular differentiation and transport capabilities in uterine luminal as well as glandular epithelium and the trophoblast.
胎盘血管生成和生长是胚胎及后期胎儿发育的关键要素。血管内皮生长因子（VEGF）及其特异性受体Flt-1（VEGFR-1）和KDR（VEGFR-2）构成了参与血管生成和微血管高通透性的强大配体-受体系统。在本免疫组织化学研究中，VEGF、Flt-1和KDR在整个妊娠期的周期性非妊娠母猪子宫及猪上皮绒毛膜胎盘中均有定位。重点关注妊娠早期阶段，形态学研究表明在此初始胎盘形成过程中存在广泛的血管生成。结果显示配体及其受体在时空分布上高度相关，并且在几种非内皮细胞中意外地发现了VEGF受体。在非妊娠母猪中，VEGF、Flt-1和KDR在子宫腔上皮和血管壁平滑肌细胞中呈现中度至强染色。动脉和小动脉的内皮细胞显示Flt-1和KDR标记，而子宫腺上皮在黄体后期显示强烈的KDR免疫反应性。在妊娠期，子宫腔上皮在妊娠早期前半段[交配后（p.c.）≤21天]显示出弱的配体和受体免疫染色，而后期阶段（p.c.≥21天）则显示强烈的免疫标记。血管壁的内皮细胞、平滑肌细胞和子宫腺上皮在整个妊娠期均显示强烈的配体和受体免疫反应性。在胎盘的胎儿部分，VEGF、Flt-1和KDR免疫染色在整个妊娠期滋养层中呈现中度至强反应性，但在妊娠早期后半段（p.c.21 - 30天）除外。胎儿血管壁对VEGF、Flt-1和KDR也呈免疫阳性。综上所述，结果表明VEGF、Flt-1和KDR配体-受体系统参与了猪胎盘形成的调节，并且除了其血管生成特性外，还可能影响子宫腔及腺上皮和滋养层中的细胞分化及转运能力。
