Investigation for congenital anomaly. Relationship with diabetes mellitus and endocrine-disrupting chemical

过量葡萄糖激活二酰基甘油-蛋白激酶C（DAG-PKC）级联反应与糖尿病血管并发症有关。它与糖尿病胚胎病的关系尚未确定。我们研究了DAG生产和蛋白激酶C活性在胚胎和蜕膜的链脲佐菌素（STZ）糖尿病或短暂性高血糖小鼠在神经管形成。STZ糖尿病显着增加DAG和总PKC活性在第9.5天的蜕膜和胚胎。膜相关PKC α、β II、δ和zeta在蜕膜中增加1.25- 2.8倍。母体高血糖诱导的葡萄糖注射在第7.5天，神经管形成的发病前一天，也增加DAG，PKC活性，和PKC亚型在胚胎中的第9.5天。这些数据表明，器官形成前的高血糖激活DAG-PKC级联反应，并与先天性缺陷有关。在糖尿病小鼠胎盘中，过氧化物酶体增殖物激活受体γ（PP）的表达， ...更多信息 与正常胎盘比较，ARγ、VEGF表达明显增加。在体外研究中，高糖条件增强了PPARγ的表达和hCG的产生，但抑制了细胞增殖。在高糖条件下，加入PPARγ配体减弱了这种作用。虽然高糖条件不影响VEGF的产生，但在正常和高糖条件下，PPARγ配体促进VEGF的产生。这些数据表明，PPARγ及其靶基因VEGF在胎盘发生中发挥作用，特别是在糖尿病妊娠期间。PPARγ配体可以消除高糖条件下对胎盘发育的损害，VEGF可能参与了这一通路，我们提出证据表明内分泌干扰物（EDCs）双酚A和邻苯二甲酸酯通过与TRAP 220相互作用激活雌激素受体（ER）介导的转录。此外，与邻苯二甲酸酯和雌二醇相比，双酚A对子宫组织中ER-β和TRAP 220之间的相互作用以及ER-β和TRAP 220的表达具有积极影响。这些结果表明，某些内分泌干扰物可能通过改变子宫内膜组织中受体和辅激活因子的水平，以及对ER与辅激活因子TRAP 220相互作用的不同影响，从而改变内分泌功能。滋养层细胞内有少量的细胞色素沉着。AGEs以时间和剂量依赖性方式显著刺激滋养细胞分泌MIP-1 α和MIP-1 β。AGEs可显著诱导细胞凋亡，减少hCG分泌。AGEs引起的MIP-1 α和MIP-1 β分泌增加可被一氧化氮合酶（NOS）抑制剂或甲磺酸萘莫司他显著抑制。这些药物还抑制AGEs对hCG分泌和滋养细胞凋亡的影响。本研究观察了链脲佐菌素诱导的糖尿病妊娠大鼠血液流变学的变化。糖尿病合并高血压孕鼠红细胞压积、100μl全血毛细血管模型瞬时时间、全血粘度增高。他们的胎儿生长受限

Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade by excess glucose has been implicated in vascular complications of diabetes. Its involvement in diabetic embryopathy has not been established. We examined DAG production and PKC activities in embryos and decidua of streptozotocin (STZ)-diabetic or transiently hyperglycemic mice during neural tube formation. STZ diabetes significantly increased DAG and total PKC activity in decidua and embryos on day 9.5. Membrane-associated PKC alpha, betaII, delta, and zeta were increased in decidua by 1.25- to 2.8-fold. Maternal hyperglycemia induced by glucose injection on day 7.5, the day before the onset of neural tube formation, also increased DAG, PKC activity, and PKC isoforms in the embryo on day 9.5. These data indicate that hyperglycemia just before organogenesis activates the DAG-PKC cascade and is correlated with congenital defects.In diabetic mouse placenta, the expression of peroxisome proliferator-activated receptorγ(PP … More ARγ) and VEGF increased compared with that in normal placenta. In an in vitro study, the high glucose condition enhanced the PPARγ expression and hCG production, but suppressed cell proliferation. The addition of PPARγ ligands diminished the effects under the high glucose condition. Although the high glucose condition didn't affect VEGF production, the PPARγ ligands enhanced it under normal and high glucose conditions. These data suggest PPARγ and its target gene, VEGF, play a role in placentogenesis, especially during diabetic pregnancy. PPARγ ligands can eliminate the impairment of placental development induced by high glucose conditions, and VEGF might be involved in this pathway.We present evidence that the endocrine-disrupting chemical (EDCs) bisphenol A and phthalate activate estrogen receptor (ER) -mediated transcription through interaction with TRAP220. Moreover, bisphenol A had positive effects on the interaction between ER-beta and TRAP220 and on the expression of ER-beta and TRAP220 compared with phthalate and estradiol in uterine tissue. These data suggested that some EDCs might alter endocrine function through the change of the receptor and coactivator levels in uterine tIssue and through the different effect on the interaction between ERs and coactivator TRAP220.We studied the effects of advanced glycation end products (AGEs) and its receptor (RAGE) in human trophoblasts. RAGE was localized in trophoblasts. AGEs significantly stimulated secretion of both MIP-1 alpha and MIP-1 beta from trophoblasts in a time- and dose-dependent manner. AGEs significantly induced apoptosis and reduced secretion of hCG. Increased secretions of MIP-1 alpha and MIP-1 beta by AGEs were significantly suppressed by inhibitors of nitric oxide synthase (NOS) or nafamostat mesilate. These agents also suppressed the effects of AGEs on hCG secretion and trophoblastic apoptosis. These AGE-mediated changes in trophoblasts may lead to impairment of implantation and placentation.Blood rheological changes in streptozotocin-induced diabetic pregnant rats were examined. Diabetic pregnant rats with hypertentsion showed increased hematocrit, model capillary transient time of 100μl of whole blood and whole blood viscosity. Their fetuses were growth restricted Less