REGULATION OF VEGF AND VEGF RECEPTOR EXPRESSION IN THE RODENT MAMMARY GLAND DURING PREGNANCY, LACTATION, AND INVOLUTION

Vascular endothelial growth factors (VEGFs) are endothelial cell-specific mi- togens with potent angiogenic and vascular per- meability-inducing properties. VEGF, VEGF-C, and VEGFRs -1, -2, and -3 were found to be ex- pressed in post-pubertal (virgin) rodent mam- mary glands. VEGF was increased during preg- nancy (5-fold) and lactation (15-19-fold). VEGF-C was moderately increased during pregnancy and lactation (2- and 3-fold respectively). VEGF levels were reduced by approximately 75% in cleared mouse mammary glands devoid of epithelial com- ponents, demonstrating that although the epi- thelial component is the major source of VEGF, approximately 25% is derived from stroma. This was confirmed by the findings (a) that VEGF transcripts were expressed predominantly in ductal and alveolar epithelial cells, and (b) that VEGF protein was localized to ductal epithelial cells as well as to the stromal compartment in- cluding vascular structures. VEGF was detected in human milk. Finally, transcripts for VEGFRs -2 and -3 were increased 2-3-fold during preg- nancy, VEGFRs -1, -2 and -3 were increased 2-4-fold during lactation, and VEGFRs -2 and -3 were de- creased by 20-50% during involution. These results point to a causal role for the VEGF ligand-receptor pairs in pregnancy-associated angiogenesis in the mammary gland, and suggest that they may also regulate vascular permeability during lactation. Dev Dyn 2000;218:507-524. © 2000 Wiley-Liss, Inc.