Journal
DEVELOPMENT
Volume 130, Issue 8, Pages 1713-1724Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.00403
Keywords
hypoxia; HIF; mammary gland; lactation; differentiation; metabolism; mouse
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Funding
- NCI NIH HHS [CA82515] Funding Source: Medline
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During pregnancy the mammary epithelium and its supporting vasculature rapidly expand to prepare for lactation, resulting in dramatic changes in the microenvironment. In order to investigate the role of oxygenation and metabolism in these processes, the oxygen-responsive component of the hypoxia-inducible factor (HIF) 1 complex, HIF1alpha, was deleted in the murine mammary gland. Although vascular density was unchanged in the HIF1alpha null mammary gland, loss of HIF1alpha impaired mammary differentiation and lipid secretion, culminating in lactation failure and striking changes in milk composition. Transplantation experiments confirmed that these developmental defects were mammary epithelial cell autonomous. These data make clear that HIF1alpha plays a critical role in the differentiation and function of the mammary epithelium.
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