Rutland Catrin S, Mukhopadhyay Mallinath, Underwood Suzanne, Clyde Norma, Mayhew Terry M, Mitchell Christopher A
School of Biomedical Sciences, University of Nottingham, Nottingham, NG7 2UH United Kingdom.
Biol Reprod. 2005 Dec;73(6):1164-73. doi: 10.1095/biolreprod.105.043893. Epub 2005 Aug 3.
The placenta is a specialized vascular interface between the maternal and fetal circulations that increases in size to accommodate the nutritional and metabolic demands of the growing fetus. Vascular proliferation and expansion are critical components of placental development and, consequently, interference with vascular growth has the potential to severely restrict concurrent development of both the placenta and fetus. In this study, we describe the effects of an antiangiogenic agent, TNP-470, on placental vascular development and the induction of a form of intrauterine growth restriction (IUGR) in mice. Administration of TNP-470 to dams in the second half of pregnancy resulted in a smaller maternal weight gain accompanied by decreased placental and fetal sizes in comparison with control animals. Total numbers of fetuses per litter were not affected significantly. Stereological analysis of placentas revealed no changes in the combined lengths of vessels. However, the mean cross-sectional areas of maternal and fetal vessels in the labyrinth of TNP-470-treated mice were reduced at Embryonic Day 13.5 (E13.5) but not at E18.5. Further analysis showed reduced placental endothelial proliferation at E13.5 and E18.5 in TNP-470-treated animals. No other structural or morphometric differences in placentas were detected between TNP-470-treated and control mice at E18.5. This study provides conclusive evidence that administration of TNP-470 interferes with placental vascular proliferation and vessel caliber and results in a reproducible model of IUGR.
胎盘是母体和胎儿循环系统之间的一个特殊血管界面，其大小会增大以适应不断生长的胎儿的营养和代谢需求。血管增殖和扩张是胎盘发育的关键组成部分，因此，干扰血管生长有可能严重限制胎盘和胎儿的同步发育。在本研究中，我们描述了一种抗血管生成剂TNP - 470对胎盘血管发育的影响以及在小鼠中诱导一种形式的宫内生长受限（IUGR）的情况。在妊娠后半期给母鼠施用TNP - 470，与对照动物相比，导致母体体重增加较少，同时胎盘和胎儿尺寸减小。每窝胎儿的总数没有受到显著影响。对胎盘的体视学分析显示血管总长度没有变化。然而，在胚胎第13.5天（E13.5），TNP - 470处理的小鼠迷路中母体和胎儿血管的平均横截面积减小，但在E18.5时没有减小。进一步分析表明，在E13.5和E18.5时，TNP - 470处理的动物胎盘内皮细胞增殖减少。在E18.5时，TNP - 470处理的小鼠和对照小鼠的胎盘在其他结构或形态测量方面没有检测到差异。本研究提供了确凿的证据，即施用TNP - 470会干扰胎盘血管增殖和血管口径，并导致一种可重复的IUGR模型。
