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

糖尿病母亲的婴儿先天畸形的发生率增加。尽管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20年里没有改变，这是糖尿病母亲所生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是多样和复杂的，每个因素对胎儿的影响很难在体内实验中评估。因此，我们试图建立一个大鼠全胚胎体外培养系统，使我们能够评估特定材料在器官发生时期对胎儿的影响。按New等人的方法进行全胚胎培养。妊娠第9天，将Wistar大鼠胚胎移植到培养液中，在原旋转培养机上，在37ﾟC下以60rpm的转速旋转培养48h。培养48h后，用DIREC…检测胚胎生长情况。更多的测量胚胎的头臀长度(CRL)和躯体发育。大的和轻微的畸形分别以神经损害和较轻的神经外损害为特征。通过向培养基中添加不同浓度的葡萄糖和β-羟基丁酸酯，研究了高血糖、低血糖、高酮血症等糖代谢异常所产生的各种因素的影响。高糖(300 mg/dl*)培养的胚胎CRL明显缩短，体节数明显减少。随着葡萄糖浓度的增加(300 mg/dl*)，大畸形和轻微畸形的发生率增加。低血糖48h(50 mg/dl葡萄糖)对大鼠胚胎有致病作用。在最初的24小时内暴露于低血糖环境中的胚胎比暴露在第二个24小时内的胚胎更容易发生生长迟缓和畸形发育，并且随着培养液中葡萄糖浓度的变化，这种影响会增强。暴露于高酮血症(6 mM*的β-羟基丁酸酯)的48h表现出生长迟缓和大、小畸形。高糖和β-羟丁酸的共存协同作用增强了对胎儿的不良影响。综上所述，这些发现表明高、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。较少

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