{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:00:00Z","timestamp":1767834000682,"version":"3.49.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,9]]},"abstract":"<jats:sec>\n                    <jats:title>In brief<\/jats:title>\n                    <jats:p>Formation and function of the corpus luteum strongly rely on active angiogenesis. This study demonstrates the role of the hypoxia-inducible factor (HIF) in luteinization with no effect on fertility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>HIFs are transcription factors responsible for sensing low oxygen levels and, in response, inducing the transcription of numerous genes. One of the main processes stimulated by HIFs is the formation of new vessels to increase oxygen supply to the tissue. Formation of the corpus luteum strongly depends on the vasculature, and active angiogenesis occurs during luteinization. In this study, we aimed to analyze the role of HIF in the early formation of corpus luteum and its function, and in female fertility. To this aim, we superovulated mice using equine chorionic gonadotropin and human chorionic gonadotropin (hCG) and administered the HIF inhibitor acriflavine (ACF) to the mice 3 h before hCG. We found a decrease in ovarian HIF1A and VEGFA and in the vascular area in the animals treated with ACF. Moreover, we observed an increase in aberrant structures in the ovaries and in luteal cell apoptosis. Serum progesterone levels were decreased together with ovarian STAR expression. However, the animals treated with ACF during the early formation of the corpus luteum were completely fertile and no alterations were observed when the treated females were mated with fertile males. These results collectively suggest that HIF regulates gonadotropin-induced corpus luteum formation by acting on luteal blood vessel formation, luteal cell survival and progesterone synthesis. However, adequate HIF activity may not be essential to achieve and maintain pregnancy. These findings are significant to better understand the complex mechanisms of corpus luteum formation and identify potential abnormalities to allow better knowledge of ovarian physiology and pathologies in which this factor could be involved.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/rep-24-0313","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T13:55:25Z","timestamp":1733752525000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":1,"title":["Hypoxia-inducible factor inhibition affects luteal function with no effect on fertility in mice"],"prefix":"10.1093","volume":"169","author":[{"given":"Roc\u00edo Celeste","family":"Marinoni","sequence":"first","affiliation":[{"name":"Tumor Physiology and Biology of the Ovary Laboratory, Institute of Biology and Experimental Medicine (IBYME) \u2013 National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Espa\u00f1a De Marco","sequence":"additional","affiliation":[{"name":"Tumor Physiology and Biology of the Ovary Laboratory, Institute of Biology and Experimental Medicine (IBYME) \u2013 National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candela","family":"Velazquez","sequence":"additional","affiliation":[{"name":"Studies of the Physiopathology of the Ovary Laboratory, Institute of Biology and Experimental Medicine (IBYME) \u2013 National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Prost","sequence":"additional","affiliation":[{"name":"Pedro Fiorito Hospital, Avellaneda, Buenos Aires Province, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Parborell","sequence":"additional","affiliation":[{"name":"Studies of the Physiopathology of the Ovary Laboratory, Institute of Biology and Experimental Medicine (IBYME) \u2013 National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Tesone","sequence":"additional","affiliation":[{"name":"Tumor Physiology and Biology of the Ovary Laboratory, Institute of Biology and Experimental Medicine (IBYME) \u2013 National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-8147","authenticated-orcid":true,"given":"Dalhia","family":"Abramovich","sequence":"additional","affiliation":[{"name":"Studies of the Physiopathology of the Ovary Laboratory, Institute of Biology and Experimental Medicine (IBYME) \u2013 National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Reproduction","first-page":"1","article-title":"A link between Notch and progesterone maintains the functionality of the rat corpus luteum","volume":"149","author":"Accialini P","year":"2015","unstructured":"Accialini P, Hern\u00e1ndez SF, Bas D, et al. 2015 A link between Notch and progesterone maintains the functionality of the rat corpus luteum. 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