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2 November 2022 Role of progesterone on dexamethasone-induced alterations in placental vascularization and progesterone receptors in rats
Mariam Alawadhi, Narayana Kilarkaje, Abdeslam Mouihate, Maie D. Al-Bader
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Abstract

Background: Intrauterine growth restriction (IUGR) is manifested by lower maternal progesterone levels, smaller placental size, and decreased placental vascularity indicated by lower expression of vascular endothelial growth factor (VEGF). Studies showed that progesterone increases angiogenesis and induces VEGF expression in different tissues. Therefore, the aim of the present study is to evaluate the effect of progesterone on placental vascular bed and VEGF expression and the modulation of nuclear and membranous progesterone receptors (PR) in dexamethasone-induced rat IUGR model. Methods: Pregnant Sprague–Dawley rats were allocated into four groups and given intraperitoneal injections of either saline, dexamethasone, dexamethasone, and progesterone or progesterone. Injections started on gestation day (DG) 15 and lasted until the days of euthanization (19 and 21 DG). Enzyme-linked immunosorbent assay was used to evaluate plasma progesterone levels. Real-time PCR and western blotting were used to evaluate gene and protein expressions of VEGF, and PR in labyrinth and basal placental zones. Immunohistochemistry was used to locate VEGF and different PRs in placental cells. Immunofluorescence was used to monitor the expression of blood vessel marker (αSMA). Results: Dexamethasone decreased the vascular bed fraction and the expression of VEGF in both placental zones. Progesterone co-treatment with dexamethasone prevented this reduction. Nuclear and membrane PRs showed tissue-specific expression in different placental zones and responded differently to both dexamethasone and progesterone. Conclusions: Progesterone treatment improves the outcomes in IUGR pregnancy. Progesterone alleviated DEX-induced IUGR probably by promoting placental VEGF and angiogenesis.

Summary Sentence

Dexamethasone-induced reduction in placental angiogenesis and alteration in the expression of progesterone receptor subtypes during pregnancy are partially reversed by progesterone.

Graphical Abstract

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© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Mariam Alawadhi, Narayana Kilarkaje, Abdeslam Mouihate, and Maie D. Al-Bader "Role of progesterone on dexamethasone-induced alterations in placental vascularization and progesterone receptors in rats," Biology of Reproduction 108(1), 133-149, (2 November 2022). https://doi.org/10.1093/biolre/ioac192
Received: 27 April 2022; Accepted: 18 October 2022; Published: 2 November 2022
KEYWORDS
angiogenesis
intrauterine growth restriction
labyrinth zone placenta
progesterone receptors
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