Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine secretion, and promotes macrophage differentiation in an immunocompetent mouse model of endometriosis
Retinoic acid inhibition of endometriotic-implant development in mouse model endometriosis may be related to suppression of interleukin-6 and macrophage chemotactic factor-1 production, and promotion of peritoneal macrophage differentiation.
Friedrich Wieser, M.D., Juanjuan Wu, M.D., Ph.D., Zhaoju Shen, Ph.D., Robert N. Taylor, M.D., Ph.D., Neil Sidell, Ph.D.
Volume 97, Issue 6 , Pages 1430-1437, June 2012
To determine the effects of all-trans-retinoic acid (RA) on establishment and growth of endometrial lesions, peritoneal interleukin-6 (IL-6) and macrophage chemotactic factor-1 (MCP-1) concentrations, and CD38, CD11b, and F4/80 expression on peritoneal macrophages in an immunocompetent mouse model of endometriosis.
Experimental transplantation study using mice.
Academic medical center.
C57BL/6 recipient mice and syngeneic green fluorescent protein transgenic (GFP+) mice.
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, and expression of CD11b, F4/80, and CD38 on peritoneal macrophages.
Retinoic acid treatment for 17 days reduced the number of implants versus controls and decreased the frequency of lesions with vessels. Peritoneal washings in RA-treated animals had lower concentrations of 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 versus controls.
The development of endometriotic implants is inhibited by RA. This effect may be caused, at least in part, by reduced IL-6 and MCP-1 production and enhanced differentiation of peritoneal macrophages.