Abstract 545: Response Gene to Complement 32-deficiency Causes Impaired Placental Angiogenesis in Mice
Aims The objectives of this study are to determine the role of response gene to complement 32 (RGC-32) in the placental angiogenesis during pregnancy and explore the underlying mechanisms.
Methods and Results RGC-32-deficient (RGC32-/-) mice were generated from C57BL/6 embryonic stem cells with deletion of Exon 2 and 3 of RGC-32 gene. Most of the RGC32-/- mice can survive. However, their body sizes were much smaller compared to their wild-type littermates when they were born. By examining the embryo development and placentas at 16.5 days post-coitum, we found that RGC32-/- embryos and fetal placentas were significantly smaller than the wild-type. Further analysis showed that the labyrinth zone of RGC32-/- fetal placenta was smaller with defective angiogenesis. Mechanistically, vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and placental growth factor (PlGF), but not other angiogenic factors, were significantly downregulated in RGC32-/- placentas, suggesting that VEGFR2 and PlGF may mediate RGC-32 function in placenta angiogenesis. Indeed, knockdown of RGC-32 by shRNA inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation while blocking VEGFR2 expression. Knockdown of RGC-32 also inhibited trophoblast proliferation while blocking the expression of PlGF.
Conclusion Absence of RGC-32 caused intrauterine growth restriction through interrupting the placental angiogenesis, which was due to the decreased expressions of VEGFR2 in endothelial cells and PlGF in trophoblast cells.
- Response Gene to Complement 32
- Intrauterine Growth Restriction
- Vascular Endothelial Growth Factor Receptor
- Placental Growth Factor
- © 2013 by American Heart Association, Inc.