Angiopoietin-2 regulated by progesterone induces uterine vascular remodeling during pregnancy

Park,Yang-Gyu; Choi,Jawun; Seol,Jae-Won

doi:10.3892/mmr.2020.11185

Angiopoietin-2 regulated by progesterone induces uterine vascular remodeling during pregnancy

Authors:
- Yang-Gyu Park
- Jawun Choi
- Jae-Won Seol
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Affiliations: Biosafety Research Institute and Laboratory of Biochemistry, College of Veterinary Medicine, Jeonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea
Published online on: May 27, 2020 https://doi.org/10.3892/mmr.2020.11185
Pages: 1235-1242
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

During pregnancy, the uterus undergoes intense neovascularization and vascular remodeling to supply oxygen and nutrients to the embryo. During this period, progesterone secreted from the ovary has effects on vascular remodeling in the endometrium and interacts with angiogenic factors. However, the exact mechanism of uterine vascular remodeling during pregnancy is poorly understood. Therefore, the aim of the present study was to investigate the association between angiopoietin-2 (Ang-2), one of the angiopoietins, and intrauterine vessel remodeling during pregnancy, and to determine the effect of progesterone on Ang-2 levels. Changes in Ang-2 expression were observed according to quantitative modification of progesterone using pregnant mice and human uterine microvascular endothelial cells. As a result, Ang-2 was observed mainly in the mesometrial region (MR) of the uterus during the period between implantation and placentation. Furthermore, a substantial amount of Ang-2 also appeared in endothelial cells, particularly of the venous sinus region (VSR). Interestingly, Ang-2 expression was increased by progesterone, whereas estrogen had limited effects. To confirm the association between Ang-2 and progesterone, the function of the progesterone receptor (PR) was inhibited using RU486, a blocker of PR. Ang-2 expression and vascular remodeling of the VSR in the uterus were decreased when the functions of progesterone were inhibited. Overall, the regulation of Ang-2 by progesterone/PR was associated with vascular remodeling in the VSR during pregnancy. The present study proposed a solution to prevent pregnancy failure due to a lack of vascularity in the uterus in advance.

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