Expression of VEGF 111 and other VEGF-A variants in the rat uterus is correlated with stage of pregnancy
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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, VEGF 111 , in vivo in mammals. This variant has previously only been found in mammals in cultured human cells exposed to genotoxic agents. Our discovery of VEGF 111 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 VEGF 111 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 VEGF 111 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 VEGF 111 in rat uterus paves the way for the development of in vivo models of VEGF 111 activity in a highly tractable laboratory animal, and is particularly significant in the context of early pregnancy loss and cancer research.
KeywordsAngiogenesis Implantation Pregnancy Uterus Vascular endothelial growth factor Viviparity
We thank L. Lindsay, C. Poon, R. Madawala and V. Nguyen for assistance with rat vaginal smearing, B. McAllan for generously providing dunnart tissues, and M. Laird for assisting with their collection. We are grateful to CR Friesen and JU Van Dyke for statistical advice and M. Olsson for sharing his molecular laboratory space and equipment. RNA integrity analysis was carried out in the Bosch Molecular Biology Facility at the University of Sydney.
Compliance with ethical standards
This study was funded by Australian Research Council Grant DP120100649 to MBT, CRM, and GEG, and a University of Sydney Animal and Veterinary Biosciences Research Fellowship to CMW. The funding sources had no involvement in study design, collection, analysis and interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication.
Conflict of interest
The authors declare that there are no conflicts of interest.
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