Effect of ovarian steroids on vascular endothelial growth factor a expression in bovine uterine endothelial cells during adenomyosis

Martyna Lupicka,Anna Zadroga,Agata Szczepańska,Anna Justyna Korzekwa

doi:10.1186/s12917-019-2222-0

Abstract

BackgroundAdenomyosis is a uterine dysfunction defined as the presence of endometrial glands within the myometrium. There is evidence that proangiogenic factors may play a role during the development of adenomyosis; however, exact mechanism remains unknown. The aim of the study was to determine the action of vascular endothelial growth factor A (VEGFA) in uterine tissue and uterine vascular endothelial cells during adenomyosis.ResultsUterine tissues were collected and examined for the presence and extent of adenomyosis. Gene and protein expression of VEGFA and its two receptors (VEGFR1 and VEGFR2) was evaluated with quantitative polymerase chain reaction and Western blotting, respectively, in endometrium and myometrium during adenomyosis. Immunolocalization of VEGFA and its receptors within uterine tissues during adenomyosis was also determined. In an in vitro experiment, endothelial cells from non-adenomyotic bovine uteri were treated with media conditioned by non-adenomyotic or adenomyotic uterine slices treated with 17-beta-oestradiol (E2) or progesterone (P4). Both gene and protein expression of VEGFR2 were elevated in endometrium in stages 3–4 of adenomyosis. Protein expression of VEGFA and VEGFR2 as well as VEGFA secretion were increased in endothelial cells treated with media conditioned by adenomyotic uterine slices after E2 treatment.ConclusionsResults suggest that VEGFA signalling is an important component, next to E2, that enhances VEGFA action and participates in adenomyosis development in cows.

Highlights

Adenomyosis is a uterine dysfunction defined as the presence of endometrial glands within the myometrium
Vascular endothelial growth factor A is crucial for angiogenesis regulation, and its action depends on the receptor which it binds to
In our in vitro experiment, we showed that vascular endothelial growth factor receptor 1 (VEGFR1) might be the guardian of regulation of vascular endothelial growth factor A (VEGFA) actions in the environment of increased E2 stimulation in a healthy tissue, since VEGFR1 expression was increased in endothelial cells incubated with control explants treated with both hormones, E2 and P4, while during adenomyosis this silencing mechanism was not observed, and vascular endothelial growth factor receptor 2 (VEGFR2) protein abundance was higher under E2 influence instead

Summary

Introduction

Adenomyosis is a uterine dysfunction defined as the presence of endometrial glands within the myometrium. There is evidence that proangiogenic factors may play a role during the development of adenomyosis; exact mechanism remains unknown. The aim of the study was to determine the action of vascular endothelial growth factor A (VEGFA) in uterine tissue and uterine vascular endothelial cells during adenomyosis. Adenomyosis is a uterine dysfunction defined as the presence of endometrial glands within the myometrium [1]. The condition is observed in many female mammals, including cattle [2, 3]. In women with adenomyosis or endometriosis, the P450 aromatase is expressed in endometrial tissue, which is not observed in normal endometrium [8]. 17-betaoestradiol (E2) promotes endometrial cell proliferation and new gland formation [9].

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