Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02375-6
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Funding
- Wellcome Trust [100646/Z/12/Z]
- Wellcome Trust (ISSF) [J22738]
- Academy of Medical Sciences [AMS-SGCL13]
- Wellbeing of Women [RG1820]
- Medical Research Council [G0600048, G0500047]
- MRC [G1002033, MR/N022556/1]
- Wellcome Trust [100646/Z/12/Z] Funding Source: Wellcome Trust
- MRC [G0500047, G1100356, G0600048, G1002033, MR/N022556/1, MR/N024524/1] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL13-Maybin] Funding Source: researchfish
- Medical Research Council [G1002033, MR/N022556/1, G1100356, G0500047, MR/N024524/1, G0600048] Funding Source: researchfish
- Wellbeing of Women [RG1820] Funding Source: researchfish
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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-1 alpha 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-1 alpha induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1 alpha. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1 alpha 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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