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

先天性异常的调查。

基本信息

批准号：
14571563
负责人：
HIRAMATSU Yuji
金额：
$ 2.24万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571563/
关键词：
diabetes mellitus congenital anomaly diacylglyiceroly protein kinase C PPARγ endocrine-disrupting chemical advanced glycation end products hemorheology diabetic embryopaty diabetes pregnancy diacylglycerol hemodilution feteus a

项目摘要

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

二酰基甘油蛋白激酶C（DAG-PKC）通过过量葡萄糖的激活与TS涉及胚胎病有关。在第9.5天的神经管形成的小鼠。这些数据在第9.5天的胚胎中的同工型在糖尿病小鼠PTORγ（PP…更多的ARγ）和VEGF与正常胎盘相比体外研究，高葡萄糖的条件增强了HCG的产生，但高葡萄糖的葡萄糖不含葡萄糖。由高葡萄糖条件诱导，素食与杂草相互作用。 -beta和trap220与子宫组织中的邻苯二甲醇相比。。一氧化氮合酶（NOS）或Nafamostat的抑制剂抑制了这些药物对HCG分泌和滋养细胞凋亡的影响。被检查。