Chang T I, Loeken M R
Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Semin Reprod Endocrinol. 1999;17(2):153-65. doi: 10.1055/s-2007-1016222.
Since the advent of insulin therapy for diabetes mellitus, the survival of mothers with diabetes prior to pregnancy and their offspring has greatly improved. Nevertheless, the observation that the earliest stages of organogenesis can be impaired in the offspring of women with diabetes raises the question of how abnormal fuel metabolism disturbs embryogenesis. Research into this process has been made possible in recent years by advances in molecular biology which makes it possible to study gene expression in early embryos, and by the availability of genetically engineered mutant mouse strains. Using these approaches, a model is emerging in which elevated glucose, by disturbing expression of genes which regulate embryonic development and cell cycle progression, causes premature cell death of emerging organ structures, thereby causing defective morphogenesis. Investigation into the signaling mechanisms by which excess glucose metabolism exhibits toxic effects on embryo gene expression will explain how diabetic embryopathy occurs on a molecular and cellular level, as well as increase our understanding of the role of metabolic homeostasis in proper embryonic development.
自糖尿病胰岛素治疗问世以来，妊娠前患有糖尿病的母亲及其后代的存活率有了显著提高。然而，有观察表明，糖尿病女性的后代在器官发生的最早阶段可能会受到损害，这就引发了一个问题：异常的燃料代谢是如何干扰胚胎发育的。近年来，分子生物学的进展使得研究早期胚胎中的基因表达成为可能，同时基因工程突变小鼠品系的可得性也为这一过程的研究提供了便利。利用这些方法，一个模型正在形成，即升高的葡萄糖通过干扰调节胚胎发育和细胞周期进程的基因表达，导致新出现的器官结构过早细胞死亡，从而导致形态发生缺陷。对过量葡萄糖代谢对胚胎基因表达产生毒性作用的信号机制进行研究，将从分子和细胞水平解释糖尿病胚胎病是如何发生的，同时也将增进我们对代谢稳态在正常胚胎发育中作用的理解。
