The role of hypoxia-induced genes in ovarian angiogenesis
Rina Meidan A B , Eyal Klipper A , Yulia Zalman A and Ronit Yalu AA Department of Animal Sciences, The Hebrew University of Jerusalem, The Robert H. Smith Faculty of Agriculture, Food and Environment, Rehovot 76100, Israel.
B Corresponding author. Email: rina.meidan@huji.ac.il
Reproduction, Fertility and Development 25(2) 343-350 https://doi.org/10.1071/RD12139
Submitted: 30 April 2012 Accepted: 26 July 2012 Published: 4 September 2012
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.
Additional keywords: basic fibroblast growth factor, corpus luteum, follicle, luteal endothelial cells, lutel steroidogenic cells, vascular endothelial growth factor.
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