Balkan W, Rooman R P, Hurst-Evans A, Phillips L S, Goldstein S, Du Caju M V, Sadler T W
Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599-7220.
Teratology. 1988 Jul;38(1):79-86. doi: 10.1002/tera.1420380112.
Two human serum fractions, one from normal individuals (Mr 1,150-1,310 daltons) and the other (Mr 800-1,100 daltons) from patients suffering with uremia (renal failure, azotemia), were added to the medium used to grow embryos in whole-embryo culture (WEC) beginning at the 3-5 (day 9) or 18-21 (day 10) somite stage. Both of these fractions possessed somatomedin (insulin-like growth factor) inhibitory activity. Day 9 embryos exposed to either of the serum fractions for 24 hr exhibited incomplete rotation and neural tube closure defects and were smaller than control embryos (decreased total protein content). Developmental abnormalities induced in day 10 embryos following 24 hr in culture included a marked decrease in expansion of the brain regions, hypoplasia of the first two branchial arches, and decreased amounts of total protein compared to controls. The visceral yolk sacs (VYSs) of somatomedin inhibitor (SI)-exposed conceptuses were opaque, and those from day 10 conceptuses contained significantly more protein than controls. Morphologically, the VYS endoderm cells from SI-exposed embryos contained a much higher density of "vacuoles" than controls. These results mimic those produced by exposure of conceptuses to an SI of Mr800-1,100 obtained from the serum of diabetic rats and suggest that similar substances and mechanisms are involved.
将两种人血清组分添加到用于全胚胎培养（WEC）中培养胚胎的培养基中，一种来自正常个体（分子量1150 - 1310道尔顿），另一种（分子量800 - 1100道尔顿）来自患有尿毒症（肾衰竭、氮质血症）的患者，添加从3 - 5（第9天）或18 - 21（第10天）体节期开始。这两种组分都具有生长调节素（胰岛素样生长因子）抑制活性。暴露于任一种血清组分24小时的第9天胚胎表现出旋转不完全和神经管闭合缺陷，并且比对照胚胎小（总蛋白含量降低）。培养24小时后，第10天胚胎中诱导的发育异常包括脑区扩张明显减少、前两个鳃弓发育不全以及与对照相比总蛋白量减少。暴露于生长调节素抑制剂（SI）的孕体的内脏卵黄囊（VYS）不透明，并且来自第10天孕体的VYS比对照含有明显更多的蛋白质。从形态学上看，暴露于SI的胚胎的VYS内胚层细胞中“空泡”的密度比对照高得多。这些结果与将孕体暴露于从糖尿病大鼠血清中获得的分子量800 - 1100的SI所产生的结果相似，表明涉及类似的物质和机制。
