Contribution of hypoxia-inducible factor-1α to transcriptional regulation of vascular endothelial growth factor in bovine developing luteal cells.

Vascular endothelial growth factor (VEGF)-dependent angiogenesis is crucial for corpus leteum formation and their functional maintenance in mammalian ovaries. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1α-mediated transcriptional activation contributes to the increased expression of VEGF gene in response to hypoxia in the bovine developing luteal cells (LCs). By real-time RT-PCR analysis, VEGF messenger RNA (mRNA) expression was found to significantly increase under hypoxia or treatment with desferrioxamine (DFX), cobalt chloride (CoCl(2)) or even N-carbobenzoxyl-L-leucinyl-L-leucinyl-L-norvalinal (MG-132), while these increased VEGF mRNA expressions could also be blocked by ferrous ammonium sulfate (FAS) or cis-element oligodeoxynucleotide (dsODN) transfection under hypoxia. Further analysis also found that these changes of VEGF mRNA were consistent with HIF-1α expression or HIF-1 activity. Taken together, our results indicate that VEGF is transcriptionally activated by hypoxia through HIF-1α-mediated mechanisms in LCs. This hypoxia-induced transcriptional activation may be one of the important mechanisms mediating the increase of VEGF expression in developing LCs during mammalian corpus leteum formation.