Ovary

Vascular Endothelial Growth Factor (VEGF) Production by the Monkey Corpus Luteum During the Menstrual Cycle: Isoform-Selective mRNA Expression In Vivo and Hypoxia-Regulated Protein Secretion In Vitro

Abstract
Experiments were designed to investigate the expression and regulation of vascular endothelial growth factor (VEGF) in the primate corpus luteum (CL) throughout the luteal lifespan in the natural menstrual cycle. Corpora lutea were collected during the early (ECL, day 3-5 post LH surge), mid (MCL, day 6-8), mid-late (MLCL, day 10-12), late (LCL, day 14-16), and very late (VLCL, day 17-18) luteal phase. Specific primers were designed to amplify mRNAs encoding VEGF isoforms 206, 189, 183, 165, 145 and 121. Only two cDNA products were obtained by RT-PCR and RACE; cloning and sequencing confirmed their 98% homology to the corresponding human VEGF 165 and 121 sequences. Semi-quantitative RT-PCR assays indicated that VEGF 165 mRNA levels increased (p<0.05) from ECL to MLCL, but then declined (p<0.05) by LCL. Although VEGF 121 mRNA levels were limited in ECL, they increased significantly at MCL stage (p<0.05). VEGF protein levels, as measured by Western blot, were 2-4-fold higher for VEGF 165 versus 121. Also, VEGF 165 levels were higher (p<0.05) in ECL and MCL compared to later stages. During 2-day culture, preparations of dispersed luteal cells secreted VEGF into the media; the highest levels were observed from ECL and declined (p<0.05) by LCL. Regardless of luteal stage, hypoxic conditions increased (p<0.05) VEGF levels, whereas LH exposure increased (p<0.05) progesterone, but not VEGF, in the media. These results are consistent with a dynamic, local regulation of VEGF production during the lifespan of the primate CL that is not directly controlled by LH.

Key words: Ovary • Corpus luteum • Corpus luteum function • Luteinizing hormone • Progesterone

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