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

Jacqueline A. Maybin, Alison A. Murray, Philippa T. K. Saunders, Nikhil Hirani, Peter Carmeliet and Hilary O. D. Critchley ()
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Jacqueline A. Maybin: The Queen’s Medical Research Centre, The University of Edinburgh
Alison A. Murray: The Queen’s Medical Research Centre, The University of Edinburgh
Philippa T. K. Saunders: The Queen’s Medical Research Centre, The University of Edinburgh
Nikhil Hirani: The Queen’s Medical Research Centre, The University of Edinburgh
Peter Carmeliet: KU Leuven
Hilary O. D. Critchley: The Queen’s Medical Research Centre, The University of Edinburgh

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02375-6

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