The corpus luteum is composed of a mixture of steroidogenic and non- steroidogenic cell types. Non-steroidogenic capillary endothelial cells account for more than 50% of the total cells within the corpus luteum and are critical for neovascularization of developing luteal tissue after ovulation. In many growing (malignant and non-malignant) tissues, the cytokine, vascular endothelial growth factor (VEGF), acts directly through its receptors, FMS-like tyrosine kinase 1 (FLT-1) and kinase domain receptor (KDR) to regulate endothelial cell permeability, proliferation and angiogenesis. This study was designed to determine, via reverse transcription-polymerase chain reaction (RT-PCR), whether VEGF (three isoforms, VEGF 121,165 and 189), FLT-1 and KDR mRNA are expressed in primate corpora lutea during the early (d2-4), mid (d6-8), mid-late (d10) and late (d13-14) luteal phase of the menstrual cycle (n=3-4/stage). Two specific primer pairs (nested PCR) were developed for detection of each mRNA based on known human sequences. RT-PCR yielded cDNA products of the appropriate sizes corresponding to the three forms of VEGF mRNA from corpora lutea at all stages of the luteal phase. Sequence analysis indicated that the macaque VEGF121 mRNA was 99.2% homologous to the human counterpart and the predicted protein sequences for human and macaque VEGF were identical. FLT-1 and KDR receptor mRNA was also detected in corpora lutea collected throughout the luteal phase. Sequence analysis confirmed that the receptor primers were specific and that macaque FLT-1 mRNA was 98.2% homologous to the human counterpart. This is the first study to demonstrate the presence of all components necessary for VEGF/receptor-mediated neovascularization in the developing corpus luteum. Additionally, the continued presence of VEGF, FTL-1 and KDR mRNA throughout the luteal phase suggest a broader role for this growth factor/receptor system in the corpus luteum during its lifespan in the menstrual cycle.
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