Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation

Jacqueline A. Maybin, Alison Murray, Philippa T. K. Saunders, Nikhil Hirani, Peter Carmeliet, Hilary Critchley
In: Nature Communications · 2018 · vol. 9(1) , pp. 295 · doi:10.1038/s41467-017-02375-6 · PMID:29362355 · PMC5780386 · W2784296409
article OA: gold CC0 ⤵ 52 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Physiological hypoxia stabilizes HIF-1α to drive endometrial repair during menstruation, and its absence is linked to heavy menstrual bleeding and delayed repair.

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Abstract

Heavy menstrual bleeding (HMB) is common and debilitating, and often requires surgery due to hormonal side effects from medical therapies. Here we show that transient, physiological hypoxia occurs in the menstrual endometrium to stabilise hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We report that women with HMB have decreased endometrial HIF-1α during menstruation and prolonged menstrual bleeding. In a mouse model of simulated menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of mice under hyperoxia during menses decreases HIF-1α induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1α. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1α rescues the delayed endometrial repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the endometrium and suggest its pharmacological stabilisation during menses offers an effective, non-hormonal treatment for women with HMB.

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