Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation
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Authors
Maybin, Jacqueline A
Murray, Alison A
Saunders, Philippa T K
Hirani, Nikhil
Carmeliet, Peter
Critchley, Hilary O D
Issue Date
2018-01-23
Type
Article
Language
en_US
Keywords
Endometrium , Menstruation , Cell Hypoxia
Alternative Title
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.
Description
Citation
Maybin, J. A., Murray, A. A., Saunders, P., Hirani, N., Carmeliet, P., & Critchley, H. (2018). Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation. Nature communications, 9(1), 295. https://doi.org/10.1038/s41467-017-02375-6
Publisher
Nature Communications