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Mol. Hum. Reprod. Advance Access published online on June 6, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gam040
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Retinoic acid pathway genes show significantly altered expression in uterine fibroids when compared with normal myometrium

Marina Zaitseva1, Beverley J. Vollenhoven1,2 and Peter A.W. Rogers1,3

1 Centre for Women's Health Research, Monash University Department of Obstetrics and Gynaecology, Monash Institute of Medical Research, Clayton, Victoria, Australia 2 Women's and Children's Program, Southern Health, Melbourne, Victoria, Australia

3 Correspondence address. Tel: +61 3 9594 5379; Fax: +61 3 9594 6389; E-mail: peter.rogers{at}med.monash.edu.au

Fibroids are benign neoplasms of myometrial smooth muscle cells (SMC). Despite being the most common tumor in humans, their etiology is poorly understood. Recent microarray studies have demonstrated that multiple members of the retinoid pathway are differentially expressed between myometrium and fibroids. The aim of this present study was to investigate gene expression of members of the retinoid pathway in matched myometrium and fibroids. We have demonstrated differential gene expression of two binding proteins [cellular retinol-binding proteins (CRBP) 1 and 2], three enzymes [alcohol dehydrogenase 1 (ADH1), aldehyde dehydrogenase (ALDH1) and retinol dehydrogenase (RODH)] and two receptors [retinoid X receptors (RXR) {alpha} and {gamma}] involved in the retinoid pathway by real-time PCR. There were no differences in gene expression for retinoid receptors RAR{alpha}, ß, {gamma} and RXRß, and for the metabolizing enzyme cytochrome P450, family 26 subfamily A. We confirmed results for ADH1, ALDH1, CRBP1 and CRABP2 at the protein level by western blot. Using immunohistochemistry these proteins were mostly localized to myometrium and fibroids SMC. An exception to this was ALDH1 protein, which displayed strong staining localized to cells of the connective tissue, presumably fibroblasts, with a striking differential expression pattern between myometrium and fibroids. These results demonstrate that the retinoid pathway is altered in fibroids when compared with normal myometrium and specifically identify ALDH1 in fibroid fibroblasts. These alterations can lead to aberrant retinoic acid (RA) production and signaling, and alter the expression of RA target genes, which may be an important step in fibroid development.

Key Words: fibroids/retinoic acid pathway/ALDH1/CRBP1/CRABP2

Submitted on February 20, 2007; resubmitted on April 18, 2007; accepted on April 23, 2007.


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M. Zaitseva, B. J. Vollenhoven, and P. A.W. Rogers
Retinoids regulate genes involved in retinoic acid synthesis and transport in human myometrial and fibroid smooth muscle cells
Hum. Reprod., May 1, 2008; 23(5): 1076 - 1086.
[Abstract] [Full Text] [PDF]


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