Embryopathy in experimental diabetic gestation:: assessment of PGE2 level, gene expression of cyclooxygenases and apoptosis

被引:9
作者
El-Bassiouni, EA
Helmy, MH
Abou Rawash, N
El-Zoghby, SM
Kamel, MA
Abou Raya, AN
机构
[1] Univ Alexandria, Inst Med Res, Dept Biochem, Alexandria, Egypt
[2] Univ Alexandria, Inst Med Res, Dept Pharmacol, Alexandria, Egypt
[3] Univ Alexandria, Inst Med Res, Dept Appl Med Chem, Alexandria, Egypt
[4] Univ Alexandria, Fac Med, Dept Internal Med, Alexandria, Egypt
关键词
apoptosis; cyclooxygenases; diabetes mellitus; fetal development; prostaglandins; teratogens;
D O I
10.1080/09674845.2005.11732704
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 [基础医学];
摘要
The causes of, and predisposing conditions for, increased congenital anomalies in embryos of experimental diabetic gestation are not fully identified. In the present study, some possible factors involved in diabetes-induced embryopathy are explored. The concentration of PGE(2), the gene expression of cyclooxygenases (COX-1 and COX-2) and level of apoptosis (measured by caspase-3 activity) are assessed during organogenesis in the embryos of streptozotocin-induced diabetic rats. The concentrations of PGE(2), in the embryos of diabetic rats were lower than controls, with the lowest values in malformed embryos and their associated membranes (yolk sacs). The pattern of change in PGE2 was similar in the embryos of the control and diabetic groups, which showed a steady decline between days 9 and 11 of gestation. These changes in PGE(2), were accompanied by a small decrease in COX-1 expression in all embryos and associated membranes during the same gestational period. Expression of COX-2, which was below normal in diabetic embryos, decreased between days 9 and 11 of gestation in all groups. In the membranes of non-malformed embryos, COX-2 expression peaked on day 10 of gestation. It was found that there was little or no detectable COX-2 expression in the membranes of malformed embryos on day 9 of gestation and although its expression was detectable on the following days it was much lower than in the other groups. Caspase-3 activity increased substantially between days 9 and 11 of gestation. Embryos from the experimentally diabetic group showed higher activity than did controls, with the largest increases in the malformed embryos. It would appear that COX-2 expression and PGE(2), concentration (in both embryo and associated membranes) play a significant role in organ formation. The data presented here suggest that an unhealthy placenta may be instrumental in the development of malformed embryos.
引用
收藏
页码:161 / 165
页数:5
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