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Author Notes:

Correspondence: Neil Sidell, Ph.D., Department of Gynecology & Obstetrics, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322; Tel: 404-727-9155; Fax: 404-727-8615; Email: nsidell@emory.edu

Acknowledgments: The authors thank Jie Yu for her expert advice in animal handling and technical assistance in some of the experiments.

Disclosures: The authors have nothing to disclose

Subject:

Research Funding:

NIH R01HD55379, 1R21HD065115-01, U54HD55787, UO1HD66439

Keywords:

  • endometriosis
  • retinoic acid
  • cytokines
  • GFP-transgenic mice

Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine secretion, and promotes macrophage differentiation in an immunocompetent mouse model of endometriosis

Tools:

Journal Title:

Fertility and Sterility

Volume:

Volume 97, Number 6

Publisher:

, Pages 1430-1437

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Objective To determine the effects of retinoic acid (RA) on establishment and growth of endometrial lesions, peritoneal IL-6 and MCP-1 concentrations, and CD38, CD11b, F4/80 expression on peritoneal macrophages in an immunocompetent mouse model of endometriosis. Design Experimental transplantation study using mice. Setting Academic medical center. Animals C57BL/6 recipient mice and syngeneic Green Fluorescent Protein transgenic (GFP+) mice. Intervention(s) Recipient mice were inoculated with GFP+ minced uterine tissue to induce endometriosis and treated with RA (400 nmol/day) or vehicle for 17 days (3 days before to 14 days after tissue injection). Main Outcome Measure(s) Total number of GFP+ implants in recipient mice, number of implants showing visible blood vessels, total volume of established lesions per mouse, concentrations of IL-6 and MCP-1 in peritoneal fluid, expression of CD11b, F4/80 and CD38 on peritoneal macrophages. Results 17 days of RA treatment reduced the number of implants versus controls and decreased the frequency of lesions with vessels. Peritoneal washings in RA-treated animals had lower IL-6 and MCP-1 than controls 3 days after endometrial inoculation and lower levels of IL-6 on day 14 after inoculation. Concomitant with these effects on day 14, CD38, CD11b, and F4/80 were higher on macrophages from RA-treated mice vs. controls. Conclusions RA inhibits the development of endometriotic implants. This effect may be caused, at least in part, by reduced IL-6 and MCP-1 production and enhanced differentiation of peritoneal macrophages.

Copyright information:

© 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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