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Resveratrol and Endometrium: A Closer Look at an Active Ingredient of Red Wine Using In Vivo and In Vitro Models

Authors
  • Amaya, S. C.1
  • Savaris, R. F.2, 3
  • Filipovic, C. J.1
  • Wise, J. D.1, 4
  • Hestermann, E.1
  • Young, S. L.3
  • Lessey, B. A.1
  • 1 Greenville Health System, 890W. Faris Rd, Suite 470, Greenville, SC, 29605, USA , Greenville (United States)
  • 2 Universidade Federal do Rio Grande do Sul, Brazil , (Brazil)
  • 3 University of North Carolina at Chapel Hill, NC, USA , (United States)
  • 4 Furman University, Greenville, SC, USA , Greenville (United States)
Type
Published Article
Journal
Reproductive Sciences
Publisher
SAGE Publications
Publication Date
Nov 01, 2014
Volume
21
Issue
11
Pages
1362–1369
Identifiers
DOI: 10.1177/1933719114525271
Source
Springer Nature
Keywords
License
Yellow

Abstract

Resveratrol is a natural phytoestrogen with antiproliferative properties present in red wine, grapes, and berries. Published reports on the effects of resveratrol in human endometrial function are limited. The objective of this study was to investigate the expression of estrogen receptor α (ESR1), Ki-67 (a proliferative marker), aryl hydrocarbon receptor (AhR), and members of the cytochrome P450 superfamily of enzymes (CYP1A1 and CYP1B1) in an in vitro and vivo assay. Alkaline phosphatase assay of estrogenicity was used to compare estrogen activity of different concentrations of resveratrol to estradiol (E2) and diethylstilbestrol (DES), using Ishikawa cell culture. Immunohistochemical expression of ESR1 and Ki67, and reverse transcriptase polymerase chain reaction of AhR, CYP1A1, and CYP1B1 were analyzed from xenograft implants of human endometrial tissue in ovariectomized immunodeficient RAG-2-γ(c) mice, after 30 days of treatment with subcutaneous pellets of E2, E2 plus progesterone (P4), or E2 plus resveratrol (6, 30, or 60 mg) for 30 days. Compared to E2, resveratrol acted as an agonist and antagonist of estrogen in low and high concentrations, respectively, when combined with E2. Xenografts of human endometrial tissues in RAG-2 mice exhibited reduced expression of ESR1 and proliferative activity (Ki67) with 60 mg of resveratrol. This study suggests that resveratrol, at high doses, has the potential benefit to reduce proliferation of human endometrium through ESR1.

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