Section on Developmental and Stem Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.
Apoptosis. 2009 Dec;14(12):1472-83. doi: 10.1007/s10495-009-0338-6.
Birth defects resulting from diabetic pregnancy are associated with apoptosis of a critical mass of progenitor cells early during the formation of the affected organ(s). Insufficient expression of genes that regulate viability of the progenitor cells is responsible for the apoptosis. In particular, maternal diabetes inhibits expression of a gene, Pax3, that encodes a transcription factor which is expressed in neural crest and neuroepithelial cells. As a result of insufficient Pax3, cardiac neural crest and neuroepithelial cells undergo apoptosis by a process dependent on the p53 tumor suppressor protein. This, then provides a cellular explanation for the cardiac outflow tract and neural tube and defects induced by diabetic pregnancy.
糖尿病孕妇所生育的婴儿若有出生缺陷，通常是由于在受影响的器官形成早期，大量祖细胞发生凋亡所致。祖细胞活力相关基因表达不足是导致细胞凋亡的原因。具体来说，母体糖尿病会抑制编码转录因子 Pax3 的基因表达，而 Pax3 存在于神经嵴和神经上皮细胞中。由于 Pax3 不足，心脏神经嵴和神经上皮细胞通过依赖 p53 肿瘤抑制蛋白的过程发生凋亡。这为糖尿病孕妇生育的婴儿出现心脏流出道和神经管缺陷提供了细胞层面的解释。
