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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Aryl Hydrocarbon Receptor Nuclear Translocator, Basic Helix-Loop-Helix Transcription Factors, Blotting, Western, Cell Hypoxia, Cells, Cultured, DNA-Binding Proteins, Endometrium, Endothelial Growth Factors, Female, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Immunohistochemistry, Isoenzymes, Lymphokines, Matrix Metalloproteinases, Matrix Metalloproteinases, Membrane-Associated, Menstruation, Metalloendopeptidases, Receptors, Aryl Hydrocarbon, Stromal Cells, Trans-Activators, Transcription Factors, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors.
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Do expression of hypoxia-inducible factors in human endometrium and suppression of matrix metalloproteinases under hypoxic conditions support a major role for hypoxia in regulating tissue breakdown at menstruation? Context: Classical studies in monkeys suggested that menstruation results from vasoconstriction, hypoxia and necrosis. The heterodimeric hypoxia-inducible factor (HIF) complex is critical in oxygen homeostasis via increased stability of HIF-1alpha/2alpha monomers, and these act as markers of hypoxia. We hypothesized that focal hypoxia in perimenstrual endometrium results in locally increased matrix metalloproteinases (MMP), leading to tissue destruction. HIF-1alpha, HIF-2alpha and HIF-1beta were immunolocalized in cycling endometrium. Endometrial stromal cells were cultured under hypoxic and normoxic conditions and MMP measured by zymography and Western blots. HIF-1alpha and HIF-2alpha were detected in only some endometrial samples, and not confined to the perimenstrual tissue. Where present, they were primarily cytoplasmic, not nuclear. HIF-1beta was localized in epithelium, leukocytes and some decidual cells. Cultured endometrial stromal cells responded to hypoxia with increased cellular HIF-1alpha and secreted vascular endothelial growth factor. ProMMP-1 and proMMP-3 production was reduced in response to hypoxia regardless of the steroidal milieu (no added steroids, estrogen or estrogen plus progesterone). Active MMP-2 and membrane type 1 MMP but not proMMP-2 or proMMP-9 production were also inhibited by hypoxia.
assistant
These results do not support a role for hypoxia in the focally increased production and activation of MMP observed prior to and during menstruation. Final Decision: no