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Molecular Human Reproduction, Vol. 5, No. 5, 452-458, May 1999
© 1999 European Society of Human Reproduction and Embryology

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

Jan Steffen Krüssel1,2,3, Eva Maria Casañ2, Francisco Raga2, Jens Hirchenhain1, Yan Wen2, Hong-Yuan Huang2, Peter Bielfeld1 and Mary Lake Polan2

1 Department of Obstetrics and Gynecology, Heinrich-Heine-University Medical Center, Moorenstraße 5, D-40225 Düsseldorf, Germany, and 2 Department of GYN/OB, Reproductive Immunology Laboratory, Stanford University Medical Center, Palo Alto, CA, USA

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.

angiogenesis/cytokines/gene expression/growth factors/implantation

3 To whom correspondence should be addressed

* This work was presented in part at the 45th meeting of the Society for Gynecologic Investigation, Atlanta, GA, USA


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