{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T12:55:55Z","timestamp":1770468955838,"version":"3.49.0"},"reference-count":59,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["J.A.M.: 100646\/Z\/12\/Z"],"award-info":[{"award-number":["J.A.M.: 100646\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["ISSF fund J22738"],"award-info":[{"award-number":["ISSF fund J22738"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["J.A.M.: AMS-SGCL13"],"award-info":[{"award-number":["J.A.M.: AMS-SGCL13"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000325","name":"Wellbeing of Women","doi-asserted-by":"publisher","award":["J.A.M.: RG1820"],"award-info":[{"award-number":["J.A.M.: RG1820"]}],"id":[{"id":"10.13039\/501100000325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["H.O.D.C.: G0600048"],"award-info":[{"award-number":["H.O.D.C.: G0600048"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0500047"],"award-info":[{"award-number":["G0500047"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC Centre grants","award":["G1002033"],"award-info":[{"award-number":["G1002033"]}]},{"name":"MRC Centre grants","award":["MR\/N022556\/1"],"award-info":[{"award-number":["MR\/N022556\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Heavy menstrual bleeding (HMB) is common and debilitating, but the precise endometrial mechanisms causing increased menstrual blood loss (MBL) remain undefined. We have previously identified a role for hypoxia in endometrial repair following progesterone withdrawal.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>As hypoxia inducible factor 2 alpha (HIF2A) is known to alter vascular function in other tissues, we hypothezised that endometrial HIF2A is involved in premenstrual optimization of endometrial function during the secretory phase to limit MBL.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Women with objective HMB had higher endometrial HIF2A during the mid-secretory phase when compared to those with normal MBL (P = 0.0269). In a mouse model of simulated menses, genetic or pharmacological manipulation of HIF2A did not significantly affect endometrial breakdown\/repair, volume of MBL or endometrial hypoxia. However, 88% of Hif2a heterozygote mice reached early-full repair by 24 hours vs only 65% of wild-type mice. Mean MBL was 0.39\u2005\u03bcL (\u00b10.67) in Hif2a heterozygote mice vs 0.98\u2005\u03bcL (\u00b10.79) in wild-type mice. Conversely, when we increased HIF2A before menstruation, 11% reached early repair by 8 hours vs 30% of vehicle-treated mice. Mean MBL was 2.61\u2005\u03bcL (\u00b11.10) in mice with HIF2A stabilization and 2.24\u2005\u03bcL (\u00b11.14) in vehicle-treated mice. These nonsignificant but consistent trends indicate that increased endometrial HIF2A may contribute to delayed endometrial repair and HMB.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Increased HIF2A in the secretory endometrium is unlikely to be sufficient to account for the phenotype of HMB, but limitation of HIF2 levels may optimize endometrial function at menstruation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae630","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T02:36:44Z","timestamp":1726022204000},"page":"1135-1147","source":"Crossref","is-referenced-by-count":3,"title":["Limiting Premenstrual Endometrial Hypoxia Inducible Factor 2 Alpha May Fine-Tune Endometrial Function at Menstruation"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5809-3623","authenticated-orcid":false,"given":"Roc\u00edo","family":"Mart\u00ednez-Aguilar","sequence":"first","affiliation":[{"name":"Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh, EH16 4UU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6817-4543","authenticated-orcid":false,"given":"Bethan M","family":"Rowley","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh, EH16 4UU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Walker","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh, EH16 4UU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-4044","authenticated-orcid":false,"given":"Hilary O D","family":"Critchley","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh, EH16 4UU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7961-1821","authenticated-orcid":false,"given":"Peter","family":"Carmeliet","sequence":"additional","affiliation":[{"name":"Laboratory of Angiogenesis and Vascular Metabolism, VIB-KU Leuven Center for Cancer Biology , Leuven, 3000 ,","place":["Belgium"]},{"name":"Center for Biotechnology, Khalifa University of Science and Technology , Abu Dhabi, CF9X+CP9 ,","place":["United Arab 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