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| Status |
Public on Dec 19, 2009 |
| Title |
The PKA Pathway of Endometrial Stromal Fibroblasts Reveals Differentiation and Proliferative Potential in Endometriosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Intrinsic abnormalities in transplanted eutopic endometrium are believed to contribute to the pathogenesis of pelvic endometriosis. Herein, we investigated transcriptomic differences in human endometrial stromal fibroblasts (hESF) from women with (hESFendo) versus without (hESFnon-endo) endometriosis, in response to activation of the PKA pathway with 8-Br-cAMP. hESFnon-endo (n=4) and hESFendo (mild endometriosis, n=4) were isolated from eutopic endometrium and treated +/- 0.5mM 8-Br-cAMP for 96 hours. Purified total RNA was subjected to microarray analysis using the whole genome Gene 1.0 ST Affymetrix platform. 733 genes were regulated in cAMP-treated hESFnon-endo versus 172 genes in hESFendo, suggesting a blunted response to cAMP/PKA pathway activation in women with disease. Real-time PCR and ELISA validated the decreased expression of decidualization markers in hESFendo compared to hESFnon-endo. In the absence of disease, 8-Br-cAMP down-regulated progression through the cell-cycle due to a decrease in Cyclin D1, cyclin-dependent kinase 6 and cell division cycle 2, and an increase in cyclin-dependent kinase inhibitor 1A. However, cell cycle components in hESFendo were not responsive to 8-Br-cAMP, resulting in persistence of a proliferative phenotype. hESFendo treated with 8-Br-cAMP exhibited altered expression of immune response, extracellular matrix, cytoskeleton, and apoptosis genes. Changes in phosphodiesterase expression and activity were not different among experimental groups. Thus, eutopic hESF with increased proliferative potential may seed the pelvic cavity via retrograde menstruation and promote establishment, survival, and proliferation of endometriosis lesions, independent of hydrolysis of cAMP and likely due to an inherent abnormality in the PKA pathway in the presence of disease.
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| Overall design |
Endometrial tissue biopsies were obtained from 14 reproductive age women. Six subjects had endometriosis (n=1 minimal, n=2 mild, n=1 moderate-severe, n=2 severe), based on visualization of lesions during laparoscopy and their histologic evaluation. Staging of endometriosis was according to the revised American Fertility Society classification system. Participating subjects with endometriosis were 22-46 years old (mean 33.5+/-3.0), not pregnant, and did not use hormonal medications within 3 months before surgery. Controls were eight cycling premenopausal subjects (37-49 years old, mean 44.4+/-1.7) undergoing endometrial biopsy or hysterectomy for benign reasons, such as fibroids, pelvic organ prolapse, pelvic pain or endometrial polyps. Controls had regular menstrual cycles (25-35 days), were documented not to be pregnant, had no history of endometriosis and no evidence of endometriosis at laparoscopy and had not been on hormonal therapies for at least 3 months before tissue sampling.
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| Contributor(s) |
Aghajanova L, Horcajadas JA, Weeks JL, Esteban FJ, Nezhat CN, Conti M, Giudice LC |
| Citation(s) |
20068008 |
| Submission date |
Aug 05, 2009 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Jose Antonio Martinez-Conejero |
| E-mail(s) |
josn.mc@gmail.com
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| Organization name |
iGenomix
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| Street address |
C/ Guadassuar 1, bajo
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| City |
Valencia |
| ZIP/Postal code |
46015 |
| Country |
Spain |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA118917 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17504_RAW.tar |
88.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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