Vascular endothelial growth factor (VEGF) is a vital angiogenic factor which must be tightly regulated for successful blastocyst implantation and pregnancy to occur. VEGF exists as multiple isoforms, with varying roles within the uterus which all must be appropriately expressed through pregnancy. The rat ovarian hyperstimulation (OH) model provides a novel approach to study uterine changes that occur in response to superovulation protocols, and how this alters VEGF levels and the resulting vasculature.
During normal pregnancy in the rat, VEGF is required for the vascular remodelling, vascular permeability and stromal decidualisation that are necessary for successful implantation, but which are abnormal or absent following OH protocols. Thus, this study focused on the uterine expression levels of the major VEGF isoforms and its main receptor, VEGFR-2, at the time of implantation in both normal and OH pregnancies. The vascular changes occurring in the endometrium were also examined at this time.
This study showed that VEGF188, the major isoform believed to be involved in the endometrial changes throughout pregnancy, is reduced at the time of implantation in OH compared to normal pregnancy as were the levels of VEGFR2. No changes were seen in VEGF164 and VEGF120 levels. At the time of implantation in OH, vessels were significantly larger with dilated lumens, believed to be due to the decreased levels of VEGF188, which is typically involved in the formation of smaller vessels. Hormonal studies on ovariectomised rats show that all three VEGF isoforms are significantly decreased by oestrogen, and to a lesser extent, progesterone, compared to control.
The decreased levels of VEGF188 and VEGFR2, as well as the atypical vascular structure observed at the time of implantation following OH, may contribute to the decrease in endometrial receptivity caused by OH, and provide further insight into regulation of endometrial angiogenesis required for successful implantation.