权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study on the mechanism of fetal dismorphogenesis from mothers with diabetes mellitus using rat whole-embryo culture system.

利用大鼠全胚胎培养系统研究糖尿病母亲胎儿畸形发生机制。

基本信息

批准号：
05671408
负责人：
HASUO Yasuyuki
金额：
$ 1.41万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

Infants of diabetic mothers have an increased incidence of congenital malformations. Although the management of diabetic pregnancy has improved, the incidence of congenital malformations has not been changed over the past two decades, which are the main cause of perinatal death in infants from diabetic mothers. Since teratogenic factors associated with diabetes are diverse and complicated, the effect of each factor on the fetus is difficult to evaluate in an in vivo experiment. Attempts were therefore made to establish an in vitro rat whole embryo culture system which allowed us to make evaluation of the effects of specific materials on the fetus during the organogenic periods. Whole embryo culture was performed according to the method of New et al. On day 9 of pregnancy, Wister strain rat's embryos were explanted into culture medium and were cultured at 37ﾟC for 48 h with rotation at 60 rpm in our original rotation cultivator. After 48-h culture, embryonal growth was assessed by direc … More t measurement of crown-to-rump length (CRL) and somitogenesis in embryos.Major and minor malformations were characterized by neural leisons and by less severe extraneural lesions, respectively. The effects of various factors being generated by abnormal carbohydrate metabolism such as hyperglycemia, hypoglycemia and hyperketonemia were then studied by adding various concentrations of glucose and beta hydrozybutylate into culture medium. The embryos from the high glucose medium (300mg/dl*) had significantly shorter CRL and fewer somites. The incidence of major and minor malformations increased as the glucose concentration increased (300mg/dl*). Hypoglycemia for 48 h (50mg/dl of glucose) exerted embryopathic effects on rat embryos. Embryos exposed to hypoglycemia during the first 24 h were more vulnerable to growth retardation and dysmorphogenesis than those exposed for another 24 h.The effects were enhanced by a flucation of glucose concentration in the culture medium. The 48 h exposure to hyperketonemia (6mM* of beta hydroxybutylate) exhibited growth retardation and major and minor malformations. The coexistence of high glucose and beta hydroxybutylate acted synergistically to enhance the adverse effects on fetus. In conclusion, these findings indicate that the higher and lower concentrations of glucose, and ketone bodies are some of the substantial components which influence embryo growth, development and abnormalitis. Less

糖尿病母亲的婴儿先天性畸形的发生率增加。虽然糖尿病妊娠的管理有所改善，但先天性畸形的发生率在过去二十年中没有改变，这是糖尿病母亲的婴儿围产期死亡的主要原因。由于与糖尿病相关的致畸因素多种多样且复杂，在体内实验中难以评估每个因素对胎儿的影响。因此，我们试图建立一个体外大鼠全胚胎培养系统，使我们能够评估特定材料对胚胎器官发生期的影响。按照New等的方法进行全胚胎培养。在妊娠第9天，将Wister系大鼠胚胎接种到培养基中，在我们的原始旋转培养器中以60 rpm的转速在37 ℃下培养48 h。培养48小时后，通过direc ...更多信息测量胚胎的顶臀长（CRL）和体节发生。主要和次要畸形分别以神经病变和不太严重的神经病变为特征。然后通过向培养基中加入不同浓度的葡萄糖和β-羟基丁酸盐来研究由异常碳水化合物代谢产生的各种因素如高血糖症、低血糖症和高酮血症的影响。高浓度葡萄糖（300 mg/dl*）培养的胚胎，其CRL显著缩短，体节数目减少。随着葡萄糖浓度增加（300 mg/dl*），严重和轻微畸形的发生率增加。低血糖（50 mg/dl葡萄糖）48 h对大鼠胚胎有明显的胚胎病效应。暴露于低血糖的胚胎在第一个24小时更容易受到生长迟缓和畸形比那些暴露了另外24小时。通过培养基中的葡萄糖浓度的波动的影响增强。暴露于高酮血症（6 mM * β-羟基丁酸盐）48 h后，表现出生长迟缓以及严重和轻微畸形。高糖与β-羟基丁酸酯共存时，二者协同作用，加重了对胎儿的不良影响。这些结果表明，较高和较低浓度的葡萄糖和酮体是影响胚胎生长、发育和畸形的重要成分。少