Abstract：
Placentas control the maternal-fetal transport of nutrients and gases. Placental reactions to adverse intrauterine conditions affect fetal development. Such adverse conditions occur in pregnancies complicated by diabetes, leading to alterations in placental anatomy and physiology. In this study, streptozocin (STZ) injection produced sustained hyperglycemia during pregnancy in rats. Hyperglycemic pregnant rats had gained significantly less weight than normal pregnant rats on embryonic day 15.5. We investigated the influence of diabetes on placental anatomy and physiology. Compared with controls, the diabetic group had a markedly thicker junctional zone at embryonic day 15.5. To explore a mechanism for this abnormality, we examined Nodal expression in the junctional zone of control and diabetic groups. We found lower expression of Nodal in the diabetic group. We then investigated the expression of its target gene p27Kip1 (p27), which is related to cell proliferation. In vitro, Nodal overexpression up-regulated p27 protein levels while interfered EBAF up-regulated p27. In vivo, the expression of p27 was lower in diabetic compared with normal rats, and localization was similar between the two groups. In contrast, a higher expression of PCNA was found in diabetic versus normal placenta. Endometrial bleeding associated factor (EBAF), an up-stream molecular regulator of Nodal, was expressed at higher levels in placenta from diabetic versus normal rats. Based on these results, we speculate that the EBAF/Nodal/p27 signaling pathway plays a role in morphological change of diabetic placenta.
摘要：
胎盘控制营养和气体的母胎运输。胎盘对不良宫内状况的反应会影响胎儿发育。这种不利条件发生在妊娠合并糖尿病的情况下，导致胎盘解剖学和生理学改变。在这项研究中,链脲佐菌素（STZ）注射在大鼠怀孕期间产生持续的高血糖。在胚胎第15.5天，高血糖妊娠大鼠的体重增加明显少于正常妊娠大鼠。我们调查了糖尿病对胎盘解剖和生理的影响。与对照组相比，糖尿病组在胚胎第15.5天有明显较厚的交界区.为了探索这种异常的机制，我们检测了对照组和糖尿病组交界区的Nodal表达。我们发现Nodal在糖尿病组中的表达较低。然后我们研究了其靶基因p27Kip1（p27）的表达，这与细胞增殖有关。体外，Nodal过表达上调p27蛋白水平,同时干扰EBAF上调p27。在体内,p27在糖尿病大鼠中的表达低于正常大鼠,两组的定位相似。相比之下,PCNA在糖尿病胎盘中的表达高于正常胎盘.子宫内膜出血相关因素(EBAF),节点的上游分子调节剂，与正常大鼠相比，糖尿病大鼠胎盘中的表达水平更高。基于这些结果,我们推测EBAF/Nodal/p27信号通路在糖尿病胎盘的形态学改变中起作用。
