Cell Specific Expression of Vascular Endothelial Growth Factor Receptor-2 (Flk-1/KDR) in Developing Mice Embryo and Supporting Maternal Uterine Tissue during Early Gestation (D4-D7)

Abstract

Background: Vascular endothelial growth factor (VEGF) and the corresponding receptors play key role in vasculogenesisand angiogenesis processes. VEGF is one of the prime candidates in regulating embryo implantation byincreasing vascular permeability. VEGF receptor-2, also called Flk-1/KDR, is one of the prime receptor which isactively involved in the execution of various functions of VEGF. However, precise role of this receptor during earlygestation period is yet to be addressed. In the present study, expression of Flk-1/KDR during peri-implantation miceuterus as well as fetal-maternal tissues from day 4-day 7 (D4-D7) of gestation was investigated.Materials and Methods: In this experimental study, localization of Flk-1/KDR was investigated by immunohistochemistryand immunofluorescence techniques, in paraffin embedded tissue sections. Flk-1/KDR protein and mRNAexpressions were investigated by western blotting and quantitative reverse transcription polymerase chain reaction(qRT-PCR), respectively. Effects of ovarian steroids on expression of Flk-1/KDR were also assessed by estrogen andprogesterone antagonist treatment.Results: Uterine tissue on D4 showed strong expression of Flk-1/KDR in luminal and uterine glandular epithelium.On D5 and D6, differential expression of Flk-1/KDR was evidenced in certain cell types of the embryo, maternaltissues and fetal-maternal interface with varied intensity. Flk-1/KDR was specifically expressed in the ectoplacentalcone (EPC) and various cells of the embryo on D7. Flk-1/KDR expression was not evidenced in the estradiol-17β (E2)and progesterone (P4) antagonist treated uterus. Western blotting result revealed presence of Flk-1/KDR protein inthe all gestation days, except antagonist treated uterus. qRT-PCR analysis showed significant increase of Flk-1/KDRmRNA transcript on D6 and D7.Conclusion: Spatial-temporal expression of Flk-1/KDR during peri-implntation period in mice uterus especially in thefeto-maternal interface was observed. This spatio-temporal specificity as well as increased expression of Flk-1/KDRcould be one of the determinants for establishment of fetal-maternal cross talk during the critical period of development.

Keywords

• decidualization
• embryo
• flk-1/kdr
• implantation
• vascular endothelial growth factor