Macara L, Kingdom J C, Kaufmann P, Kohnen G, Hair J, More I A, Lyall F, Greer I A
Department of Obstetrics and Gynaecology, University of Glasgow, Scotland, UK.
Placenta. 1996 Jan;17(1):37-48. doi: 10.1016/s0143-4004(05)80642-3.
The abnormal umbilical artery Doppler waveform represented by absent end-diastolic flow velocity (AEDFV) identifies a group of preterm small-for-gestational age fetuses that are at high risk of perinatal death due to chronic fetal hypoxia. The placental ischaemia that results from inadequate trophoblast invasion of spiral arterioles leads to an assumption of placental villous hypoxia, though an alternative explanation is that the placenta fails to adequately transfer oxygen to the fetus from the intervillous space. Because oxygen transport takes place within the terminal villi, we undertook the first detailed studies of villous ultrastructure structure and immunohistochemistry in order to determine the likely origin of fetal hypoxia in this condition. Terminal villi were examined ultrastructurally using transmission electron microscopy and by immunohistochemical localization of matrix molecules (laminin and collagens I, III and IV) and a marker of cell proliferation (MIB-1), in 16 small-for-gestational age pregnancies with AEDFV in the umbilical artery [deemed to have intrauterine growth restriction (IUGR)] and in 16 gestation age-matched controls. Terminal villi from the IUGR cases were smaller in diameter (P < 0.02) and had several abnormal features in comparison with the controls; increased syncytial nuclei (P < 0.01), reduced cytotrophoblast nuclei (P < 0.01), thickened basal lamina (P < 0.01), and increased stromal deposition of collagens and laminin. The amount of proliferating cytotrophoblast was reduced in the IUGR group (P < 0.014) and the degree of capillary erythrocyte congestion within terminal villous capillaries was increased (P < 0.001). Several of the structural differences in the terminal villi of the IUGR group such as reduced cytotrophoblast proliferation and stromal fibrosis are incompatible with the prevailing view of placental hypoxia in IUGR. Rather thickening of the basal lamina and congestion of the capillaries by erythrocytes are predicted to limit oxygen transfer from the intervillous space to the fetus and may represent an equilibration of oxygen tension between intervillous space and the terminal villi. Despite the known reduction in uteroplacental blood flow in IUGR, fetoplacental blood flow is compromised to a far greater extent in the presence of AEDFV such that maternal blood leaving the placenta has a higher oxygen content than under normal circumstances.
舒张末期血流速度消失（AEDFV）所代表的异常脐动脉多普勒波形，识别出一组早产小于胎龄胎儿，他们因慢性胎儿缺氧而面临围产期死亡的高风险。滋养层对螺旋小动脉侵入不足导致的胎盘缺血，会让人认为胎盘绒毛存在缺氧，不过另一种解释是胎盘未能将氧从绒毛间隙充分转运给胎儿。由于氧转运发生在终末绒毛内，我们开展了首次关于绒毛超微结构及免疫组化的详细研究，以确定这种情况下胎儿缺氧的可能根源。利用透射电子显微镜对16例脐动脉出现AEDFV（被认为患有宫内生长受限（IUGR））的小于胎龄妊娠以及16例孕周匹配的对照者的终末绒毛进行超微结构检查，并通过免疫组化定位基质分子（层粘连蛋白以及I、III和IV型胶原）和细胞增殖标志物（MIB-1）。与对照组相比，IUGR病例的终末绒毛直径更小（P<0.02），且有一些异常特征；合体细胞核增多（P<0.01），细胞滋养层细胞核减少（P<0.01），基膜增厚（P<0.01），以及胶原和层粘连蛋白的基质沉积增加。IUGR组中增殖的细胞滋养层数量减少（P<0.014），终末绒毛毛细血管内的毛细血管红细胞充血程度增加（P<0.001）。IUGR组终末绒毛的一些结构差异，如细胞滋养层增殖减少和基质纤维化，与IUGR中胎盘缺氧的主流观点不符。相反，基膜增厚和红细胞导致的毛细血管充血预计会限制氧从绒毛间隙向胎儿的转运，并且可能代表绒毛间隙与终末绒毛之间氧张力的平衡。尽管已知IUGR中子宫胎盘血流减少，但在出现AEDFV的情况下，胎儿胎盘血流受损的程度要大得多，以至于离开胎盘的母体血液含氧量高于正常情况。
