Mol. Hum. Reprod. Advance Access originally published online on August 6, 2004
Molecular Human Reproduction 2004 10(10):719-728; doi:10.1093/molehr/gah097
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DNA microarray analysis of gene expression profiles in deep endometriosis using laser capture microdissection
1Department of Gynecology, Polyclinique de l'Hôtel-Dieu, CHU, Clermont-Ferrand, France, 2Department of Obstetrics & Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan, 3INSERM UMR 384, Faculté de Médecine, Clermont-Ferrand, 4Department of Pathology, Centre Jean Perrin, Clermont-Ferrand and 5Department of Pathology, Hôtel-Dieu, CHU, Clermont-Ferrand, France
6 To whom correspondence should be addressed at: Department of Gynecology, Polyclinique de l'Hotel-Dieu, CHU clermont-Ferrand, Bd. Léon Malfreyt 63058, Clermont-Fearrnd, Cedex 1, France. Email: sachikoma{at}aol.com
Endometriosis, a common gynecological disorder that causes infertility and pelvic pain, is defined as the presence of endometrial glands and stroma within extra-uterine sites. However, despite extensive studies its etiology and pathogenesis are not completely understood. Differentially expressed genes were investigated in epithelial and stromal cells from deep endometriosis and matched eutopic endometrium using cDNA microarrays and laser capture microdissection. Validation of results of several up- and down-regulated genes was performed by quantitative real-time RT–PCR. Our data showed that platelet-derived growth factor receptor alpha (PDGFRA), protein kinase C beta1 (PKC beta1) and janus kinase 1 (JAK1) were upregulated, and Sprouty2 and mitogen-activated protein kinase kinase 7 (MKK7) were downregulated in endometriosis stromal cells, suggesting the involvement of the RAS/RAF/MAPK signaling pathway through PDGFRA in endometriosis pathophysiology. In addition, two potential negative regulators of aromatase expression, chicken ovalbumin upstream promoter transcription factor 2 (COUP-TF2) and prostaglandin E2 receptor subtype EP3 (PGE2EP3), were downregulated in endometriosis epithelial cells, which might result in increased local production of estrogen in endometriosis epithelial cells. Furthermore, three potential candidate genes that might be involved in endometriosis related pain were identified: tyrosine kinase receptor B (TRkB) in endometriosis epithelial cells, and serotonin transporter (5HTT) and mu opioid receptor (MOR) in endometriosis stromal cells were all upregulated. One of the candidate genes, MOR, may be involved in a defective immune system in endometriosis. This study has provided new insights into endometriosis pathophysiology.
Key words: cDNA microarray/endometriosis/endometrium/laser capture microdissection
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