Buchanan T A, Freinkel N
Department of Medicine, Northwestern University Medical School, Chicago, IL.
Am J Obstet Gynecol. 1988 Mar;158(3 Pt 1):663-9. doi: 10.1016/0002-9378(88)90050-6.
We previously infused the D-glucose epimer D-mannose into pregnant rats to deliver a brief metabolic insult to the early postimplantation conceptus. This insult caused developmental anomalies and growth retardation that were apparent in the embryos 2 days later. We now report the long-range effects on intrauterine development of such a circumscribed metabolic insult during organogenesis. Ten pregnant animals were infused with D-mannose for 12 hours during early neurulation (day 9.5 to 10 of development). Ten control animals were infused with equimolar D-glucose during this same time interval. Mannose infusions produced maternal plasma mananose concentrations in the embryotoxic range; glucose infusions caused only slight and transient hyperglycemia. Fetuses were removed at term and examined for evidence of developmental anomalies and growth retardation. None of 137 fetuses from the mannose group or 138 fetuses from the glucose group exhibited gross anomalies. However, an excess of resorbed conceptions in the mannose group (21 versus six in the glucose group; p less than 0.01) suggested some lethal toxicity from mannose exposure during embryogenesis. Among viable fetuses, the mean body weight of those from the mannose group was significantly reduced compared with those from the glucose group (5.62 +/- 0.04 versus 5.89 +/- 0.03 gm, respectively; p less than 0.001). Reductions of a similar magnitude were noted in the mean wet weight and protein content of fetal brains, hearts, livers, and kidneys from the mannose group (range, 3.4% to 7.1% below the glucose group), indicating a symmetric pattern of fetal growth retardation. In addition, analysis of fetal ossification sites after Alizarin Red S staining revealed a significant delay of skeletal development in the mannose group. These results indicate that a relatively brief metabolic insult to embryos during early organogenesis may cause lethal developmental anomalies as well as growth retardation and delayed skeletal development that are manifested in the fetus at term.
我们之前给怀孕大鼠输注D - 葡萄糖的差向异构体D - 甘露糖，对植入后早期的孕体造成短暂的代谢损伤。这种损伤导致发育异常和生长迟缓，在2天后的胚胎中就很明显。我们现在报告这种在器官发生期间有限的代谢损伤对子宫内发育的长期影响。在早期神经胚形成阶段（发育第9.5至10天），给10只怀孕动物输注D - 甘露糖12小时。在相同时间间隔给10只对照动物输注等摩尔的D - 葡萄糖。输注甘露糖使母体血浆甘露糖浓度处于胚胎毒性范围内；输注葡萄糖仅引起轻微且短暂的高血糖。足月时取出胎儿，检查是否有发育异常和生长迟缓的迹象。甘露糖组的137只胎儿和葡萄糖组的138只胎儿均未出现明显异常。然而，甘露糖组吸收的孕体过多（21个，而葡萄糖组为6个；p小于0.01），表明胚胎发生期间暴露于甘露糖有一定的致死毒性。在存活胎儿中，甘露糖组胎儿的平均体重与葡萄糖组相比显著降低（分别为5.62±0.04克和5.89±0.03克；p小于0.001）。甘露糖组胎儿脑、心脏、肝脏和肾脏的平均湿重和蛋白质含量也有类似程度的降低（比葡萄糖组低3.4%至7.1%），表明胎儿生长迟缓呈对称模式。此外，茜素红S染色后对胎儿骨化部位的分析显示，甘露糖组骨骼发育明显延迟。这些结果表明，在器官发生早期对胚胎进行相对短暂的代谢损伤可能会导致致死性发育异常以及生长迟缓，并且在足月胎儿中表现为骨骼发育延迟。
