Inactivation of VEGF in mammary gland epithelium severely compromises mammary gland development and function.
To investigate the role of the angiogenic cytokine vascular endothelial growth factor (VEGF) during pregnancy and lactation, we used mice in which VEGF had been inactivated in mammary gland epithelial cells. Pups born to mutant mothers failed to thrive, displaying little milk in their stomachs. However, when they were transferred to control mothers they developed normally. Investigation of the mammary gland morphology revealed that lobulo-alveolar expansion into the fat pad was not complete in lactating mutant glands, and an accumulation of fat globules was evident in their secretory epithelium. In contrast to control glands, lactating mutant glands failed to up-regulate mRNAs for genes involved in milk secretion. Blood vessel density was comparable in pregnant mice of both groups but was only half that of controls in lactating mutant mice. FITC-labeled albumin injected intravenously (i.v.) into lactating mice extravasated rapidly and accumulated in the mammary gland epithelial cells in control animals, but was almost completely retained within the vessels in the mutants. Injection of recombinant VEGF i.v. reversed this effect. These findings demonstrate that mammary epithelium-derived VEGF is partially dispensable for angiogenesis during pregnancy and lactation, and by regulating vascular function during lactation, this factor is crucial to mammary gland differentiation and milk production.
Rossiter
Heidemarie
H
Department of Dermatology, Medical University of Vienna, Waehringer GuerA-1090 Vienna, Austria.
Barresi
Caterina
C
Ghannadan
Minoo
M
Gruber
Florian
F
Mildner
Michael
M
Födinger
Dagmar
D
Tschachler
Erwin
E
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology*; D007774:Lactation / Q000502:physiology; D008297:Male; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000378:metabolism; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse