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      Expression of mRNA for vascular endothelial growth factor transmembraneous receptors Flt1 and KDR, and the soluble receptor sflt in cycling human endometrium.

      Molecular Human Reproduction
      Adult, Biopsy, Cell Membrane, metabolism, Endometrium, cytology, physiology, Epithelial Cells, Female, Humans, Menstrual Cycle, Protein Isoforms, Proto-Oncogene Proteins, genetics, RNA, Messenger, analysis, Receptor Protein-Tyrosine Kinases, Receptors, Growth Factor, Receptors, Vascular Endothelial Growth Factor, Solubility, Stromal Cells, Vascular Endothelial Growth Factor Receptor-1

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          Abstract

          The aim of this study was to quantify and localize the mRNA expression of the vascular endothelial growth factor (VEGF) receptors Flt1, KDR and sflt, in human endometrium throughout the menstrual cycle. Since neoangiogenesis is crucial during embryonic implantation, we postulate that endometrial receptivity to VEGF may be altered during the luteal phase in order to support implantation. Human endometrium was collected and specified as early proliferative (n = 3), mid-proliferative (n = 4), late proliferative (n = 3), early secretory (n = 2), mid-secretory (n = 4), and late secretory (n = 4). Competitive reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the mRNA values throughout the menstrual cycle. Additionally, four samples were separated into epithelial and stromal-enriched cell fractions and competitive RT-PCR was carried out to specify the distribution of the mRNA expression. While mRNA for the transmembraneous receptors Flt1 and KDR was shown to be present at almost constant values throughout the menstrual cycle, the soluble receptor, sflt, had a three-fold higher level of transcription during mid-proliferative and late proliferative when compared with early proliferative and the entire secretory phase. The expression of Flt1, KDR and sflt mRNA was detected in both isolated endometrial epithelial and stromal cell fractions. In conclusion, the down-regulation of sflt, which functions as a soluble antagonist, during the luteal phase may act to sensitize the maternal endothelial receptors to angiogenetic stimuli secreted by the implanting embryo.

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