title: The role of hypoxia-induced genes in ovarian angiogenesis.
abstract: The hypoxic microenvironment that occurs in fast-growing tissue such as the corpus luteum (CL) is a major contributor to its ability to survive via the induction of an intricate vascular network. Cellular responses to hypoxia are mediated by hypoxia-inducible factor-1 (HIF-1), an oxygen-regulated transcriptional activator. HIF-1, a heterodimer consisting of a constitutively-expressed β subunit and an oxygen-regulated α subunit, binds to the hypoxia responsive element (HRE) present in the promoter regions of responsive genes. This review summarises evidence for the involvement of hypoxia and HIF-1α in CL development and function. Special emphasis is given to hypoxia-induced, luteal cell-specific expression of multiple genes (vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF-2), prokineticin receptor 2 (PK-R2), stanniocalcin 1 (STC-1) and endothelin 2 (EDN-2) that participate in the angiogenic process during CL formation.
authors.affiliation: Department of Animal Sciences, The Hebrew University of Jerusalem, The Robert H. Smith Faculty of Agriculture, Food and Environment, Rehovot 76100, Israel. rina.meidan@huji.ac.il
authors.forename: Rina
authors.initials: R
authors.lastname: Meidan
authors.forename: Eyal
authors.initials: E
authors.lastname: Klipper
authors.forename: Yulia
authors.initials: Y
authors.lastname: Zalman
authors.forename: Ronit
authors.initials: R
authors.lastname: Yalu
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology*; D003338:Corpus Luteum / Q000196:embryology / Q000378:metabolism*; D019333:Endothelin-2 / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010053:Ovary / Q000098:blood supply* / Q000196:embryology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019333:Endothelin-2; D005768:Gastrointestinal Hormones; D006023:Glycoproteins; D051793:Hypoxia-Inducible Factor 1; D009479:Neuropeptides; C423608:PROK2 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C051795:teleocalcin