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.