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Expression of Vascular Endothelial Growth Factor Isoforms and Receptors Flt-1 and KDR During the Peri-Implantation Period in the Mink, Mustela vison¹

Centre de recherche en reproduction animale, Faculté de médecine vétérinaire, Université de Montréal, St-Hyacinthe, Québec, Canada J2S 7C6

Expression of vascular endothelial growth factor (VEGF) isoforms and its receptors, Flt-1 and KDR, was investigated during the period of peri-implantation in mink, a species that displays obligate embryonic diapause. Uterine samples were collected during diapause, embryo activation, and implantation from pseudopregnant and anestrous animals and analyzed by semiquantitative reverse transcription polymerase chain reaction and immunohistochemistry. The abundance of mRNA of VEGF isoforms 120, 164, and 188 was highest during late embryo activation and at implantation. VEGF protein was localized to the glandular epithelium at all stages of peri-implantation, whereas the luminal epithelium lacked VEGF reactivity during diapause. Endometrial stroma and luminal and glandular epithelia were positive for VEGF in implanted uteri. The invasive trophoblast cells of the implanting embryo were intensively stained. High levels of VEGF mRNA in pseudopregnant uteri indicates that VEGF upregulation leading to implantation is dependent upon maternal rather than embryonic factors. The abundance of the two receptors, KDR and Flt-1, increased in the uterus during implantation. Low levels of the receptors in pseudopregnant uteri compared with those containing activated or implanted embryos indicates that the embryo regulates receptor expression. These results demonstrate VEGF and VEGF receptor expression during early gestation in mink and suggest that maternal and embryonic input regulates different aspects of the angiogenic process.

¹ This work was supported by the Natural Sciences and Engineering Research Council of Canada Discovery Grant to B.D.M.

² Correspondence: Bruce D. Murphy, Centre de Recherche en Reproduction Animale, Faculté de Médecine Vétérinaire, 3200 rue Sicotte, St-Hyacinthe, PQ, Canada J2S 7C6. FAX: 450 778 8103; murphyb{at}medvet.umontreal.ca

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