Differential expression of vascular endothelial growth factor-A isoforms in the mouse uterus during early pregnancy

While vascular endothelial growth factor (VEGF)-A mediates endometrial vascular remodelling during early pregnancy in mice, individual VEGF-A isoforms have not been investigated, despite their different biological properties. Using mice as a model, the expression of VEGF-A isoforms and receptors in the mouse uterus during early pregnancy was quantified. It was postulated that selected isoform expression would increase concurrent with increased endometrial endothelial cell proliferation at this time. Uteri were collected on days 1–5 of pregnancy and mRNA expression was quantified by quantitative reverse-transcription polymerase chain reaction, VEGF-A protein by Western blot and VEGF receptor (VEGFR)-2 by immunohistochemistry. The lowest expression of isomers Vegf120 and Vegf164 was observed on day 2 of pregnancy, increasing thereafter. Vegfr-2 mRNA expression was significantly higher on days 3–5 of pregnancy relative to days 1–2 (P < 0.05). No significant changes were noted in Vegf188, Nrp1 or Nrp2 mRNA. VEGF188 protein expression was consistently higher than other isoforms. These data demonstrate differential regulation of VEGF-A isoforms in mouse uterus during early pregnancy.During early pregnancy in all mammals, the blood vessels in the endometrium (uterine lining) undergo a process of growth and remodelling known as angiogenesis. Without appropriate angiogenesis, neither implantation nor placental development will be successful. The blood vessels in the endometrium respond to various growth factors released from the surrounding tissue. The best known of these factors is vascular endothelial growth factor (VEGF)-A, which interacts with a receptor called VEGFR-2. There are several different forms of VEGF-A (isoforms), which display different biological properties. The aim of this study was to quantify the expression of each of the isoforms (VEGF120, VEGF164 and VEGF188), as well as the receptor (VEGFR-2), in the mouse uterus during early pregnancy. We have shown that the expression of two of the VEGF-A isoforms (VEGF120 and VEGF164) and VEGFR-2 increases in the uterus during early pregnancy. This increase occurs at the same time as the blood vessels are remodelling in the endometrium. The remaining isoform (VEGF188) did not show any change in expression level during early pregnancy. These results indicate that the VEGF-A isoforms are controlled in different ways and also suggests they may have different roles in the vascular remodelling that occurs. By understanding the mechanisms that regulate the different VEGF-A isoforms, we may be better able to understand the reasons for implantation failure.