EXPRESSIONS OF HYPOXIA-INDUCIBLE FACTOR-1 alpha, VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTORS IN BOVINE ENDOMETRIUM THROUGHOUT THE ESTROUS CYCLE

Abstract

Hypoxia-inducible factor (HIF)-1α is known to be expressed and function specifically under hypoxic conditions. Blood flow to the bovine uterus has been shown to decrease starting at estrus, which might induce hypoxia. In bovine endometrium, HIF-1α protein expression tended to increase at the follicular and estrous stage and decrease thereafter, but the changes were not significant. Vascular endothelial growth factor (VEGF) participates in the regulation of endometrial function and its expression is strongly activated by HIF-1 (α and β). VEGF has four isoforms (121, 165, 189, 201) and two receptors (Flt-1, Flk-1). In the present study, we determined VEGF165 protein content and mRNA expressions of all isoforms and receptors in bovine endometrium throughout the estrous cycle. VEGF165 protein content was greatest at the early luteal stage, and decreased thereafter.VEGF121 and VEGF165 mRNA were highest at estrus, and decreased thereafter. Flt-1 mRNA expression was less at estrus, the early and developing luteal stages than at the other stages, while Flk-1 mRNA expression was higher at the mid and late luteal stages than at the early luteal stage. Furthermore, the ratio of Flt-1: Flk-1 mRNA was highest at estrus, and decreased thereafter. In bovine endometrial epithelial and stromal cells, VEGF mRNA expressions were higher when the cells were cultured under 3% O2 than when they were cultured under 20% O2. The overall findings suggest that the endometrial VEGF is regulated not only by HIF-1α, i.e. by hypoxic condition, but also by other factors, and that this growth factor locally plays a role in bovine endometrium throughout the estrous cycle. (poster)