Retinoic acid has the potential to suppress endometriosis development

Yoshiaki Yamagata; Eiichi Takaki; Masahiro Shinagawa; Maki Okada; Kosuke Jozaki; Lifa Lee; Shun Sato; Ryo Maekawa; Toshiaki Taketani; Hiromi Asada; Hiroshi Tamura; Akira Nakai; Norihiro Sugino

doi:10.1186/s13048-015-0179-6

Retinoic acid has the potential to suppress endometriosis development

Yamagata Y, Takaki E, Shinagawa M, Okada M, Jozaki K, Lee L, Sato S, Maekawa R, Taketani T, Asada H, Tamura H, Nakai A, Sugino N

Published July 31, 2015 Journal of Ovarian Research

DOI 10.1186/s13048-015-0179-6 PMID 26228249 PMC PMC4521362

RRM Academy Synopsis

Retinoic acid raised growth-brake genes in endometriosis cell cultures

Retinoic acid, the active form of vitamin A, turned up 49 genes in endometriosis cells, a lab study of cells from three women found. Many of the genes it raised are tied to slowing cell growth. Retinoic acid didn't significantly slow the cells' growth over four days. Estradiol in cultured endometriosis tissue was lower with retinoic acid, but not significantly.

Key Findings

Of 28,869 genes measured, 49 rose and only 4 fell after four days of retinoic acid in stromal cells from ovarian endometriosis cysts.
Gene-category analysis placed 10 of the changed genes in negative regulation of cell proliferation (p < 0.001).
A second method, quantitative RT-PCR, found higher activity in all 11 genes it checked, with significant differences in 7.
Estradiol in the medium of cyst-wall tissue from 4 women was lower with retinoic acid, with no significant difference from control.
Retinoic acid had no significant effect on how fast the cultured cells multiplied over four days, the authors report.

Interpretation

This is an in vitro study. Stromal cells, the supporting cells of the tissue, came from endometriosis cysts on the ovaries of three women, and cyst-wall tissue came from four women. All results come from cells and tissue grown in the lab with retinoic acid added. The authors read the gene changes as a sign that retinoic acid could help suppress endometriosis. They call for further research on how retinoic acid affects estrogen in the disease.

RRM Context

RRM approaches endometriosis as a disease to find and treat at its source. Studies like this one ask why lesion cells behave differently, here through how they handle vitamin A. Earlier work the authors cite found less retinoic acid in lesions than in the uterine lining. NaProTechnology surgery removes the lesions by excision.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Despite endometriosis is common estrogen dependent disease afflicting women in reproductive age, the pathogenesis has not been fully elucidated. Retinoic acid has various functions in cells as biologic modulator, and aberrant retinoid metabolism seems to be involved in the lesions of endometriosis. In order to evaluate the potential of all-trans retinoic acid (ATRA) for therapeutic treatment, a transcriptome analysis and estradiol measurements in cultured endometriotic cells and tissues were conducted.

Methods

The mRNA expression levels in ATRA-treated endometriotic stromal cells (ESC) isolated from ovarian endometrial cysts (OEC) were investigated. Estradiol production in OEC tissues was also investigated.

Results

In the isolated ESC culture supplemented with ATRA for four days, total RNA was extracted followed by a transcriptome analysis using GeneChip. Forty-nine genes were upregulated and four genes were down-regulated by the ATRA treatment. Many upregulated genes were associated with the negative regulation of cellular proliferation. In addition, ATRA treatment decreased the mRNA expression of 17-beta-dehydrogenase 2 (HSD17B2) which converts estradiol into estrone in a dose-dependent manner, and the ELISA measurements indicated that estradiol production in the OEC tissue was inhibited by ATRA treatment.

Conclusions

Retinoic acid has the potential to suppress endometriosis development.

Read the guide

Endometriosis Explained: Diagnosis, Excision Surgery, and the RRM Approach

Topics

Endometriosis › Medical Management › Hormonal Suppression Outcomes · Therapeutics › Hormonal Agents › Estrogen Preparations · Reproductive Endocrinology › Ovarian Hormones › Estrogen

Yoshiaki Yamagata, Eiichi Takaki, Masahiro Shinagawa, Maki Okada, Kosuke Jozaki, Lifa Lee, Shun Sato, Ryo Maekawa, Toshiaki Taketani, Hiromi Asada, Hiroshi Tamura, Akira Nakai, Norihiro Sugino

Y Yamagata, E Takaki, M Shinagawa, M Okada, K Jozaki, L Lee, S Sato, R Maekawa, T Taketani, H Asada, H Tamura, A Nakai, N Sugino

PMID 26228249 26228249 DOI 10.1186/s13048-015-0179-6 10.1186/s13048-015-0179-6 Yamagata et al. 2015, Yamagata 2015

Retinoic acid has the potential to suppress endometriosis development

Retinoic acid raised growth-brake genes in endometriosis cell cultures

Key Findings

Interpretation

RRM Context

Abstract

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Topics

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