Expression of hypoxia-inducible factors in human endometrium and suppression of matrix metalloproteinases under hypoxic conditions do not support a major role for hypoxia in regulating tissue breakdown at menstruation

J. Zhang, L A Salamonsen
Human Reproduction · 2002 · vol. 17(2) , pp. 265–274 · doi:10.1093/humrep/17.2.265 · PMID:11821262 · W2137150062
Lab / animal OA: closed CC0 ⤵ 18 in-corpus citations
View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-08 ⓘ

Hypoxia-inducible factors were not significantly present in perimenstrual endometrium, and hypoxia suppressed rather than increased matrix metalloproteinase production in cultured stromal cells.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results do not support a role for hypoxia in the focally increased production and activation of MMP observed prior to and during menstruation.

My notes (saved in your browser only)

MeSH descriptors

Cell Hypoxia DNA-Binding Proteins Endometrium Matrix Metalloproteinases Menstruation Receptors, Aryl Hydrocarbon Trans-Activators Transcription Factors Aryl Hydrocarbon Receptor Nuclear Translocator Basic Helix-Loop-Helix Proteins Blotting, Western Cell Hypoxia Cells, Cultured Endometrium Endometrium Endothelial Growth Factors Endothelial Growth Factors Endothelial PAS Domain-Containing Protein 1 Female Humans

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (51)

Cited by (18)

Source provenance

openalex
last seen: 2026-05-13T19:46:01.794608+00:00
pubmed
last seen: 2026-10-08T21:00:15.595027+00:00
unpaywall
last seen: 2026-10-09T06:36:44.367587+00:00
License: CC0 · commercial use OK