Expression of VEGF111 and other VEGF-A variants in the rat uterus is correlated with stage of pregnancy
Vascular endothelial growth factor A is a major mediator of angiogenesis, a critically important process in vertebrate growth and development as well as pregnancy. Here we report for the first time the expression of a rare and unusually potent splice variant, VEGF111, in vivo in mammals. This variant has previously only been found in mammals in cultured human cells exposed to genotoxic agents. Our discovery of VEGF111 in the uterus of both a eutherian (rat) and a marsupial (fat-tailed dunnart) suggests that the splice variant may be common to all mammals. As VEGF111 is also expressed in the uterus of at least one lineage of lizards, the expression of this splice variant may be a widespread amniote phenomenon. We measured expression of VEGF111 and two major VEGF-A splice variants in the uterus of pregnant rats, showing that the three variants show different expression patterns across pregnancy. Our results suggest that viviparous mammals possess a precisely regulated milieu of VEGF isoforms producing the angiogenesis required for successful pregnancy. The discovery of VEGF111 in rat uterus paves the way for the development of in vivo models of VEGF111 activity in a highly tractable laboratory animal, and is particularly significant in the context of early pregnancy loss and cancer research.