Unique Transcriptome, Pathways, and Networks in the Human Endometrial Fibroblast Response to Progesterone in Endometriosis

摘要: Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P4) and activation the PKA pathway stromal compartment. To investigate global temporal responses eutopic P4, we compared early (6-h), intermediate (48-h), late (14-Day) transcriptomes, signaling pathways, networks human endometrial fibroblasts (hESF) from women with (hESFendo) hESF without (hESFnonendo). Endometrial biopsy samples were obtained subjects mild peritoneal (n = 4 per group), isolated treated P4 (1 μM) plus estradiol (E2) (10 nM), E2 alone or vehicle for up 14 days. Total RNA was subjected microarray analysis using a Gene 1.0 ST (Affymetrix) platform analyzed by bioinformatic algorithms, data validated quantitative real-time PCR ELISA. Results revealed unique kinetic expression specific genes distinct biological processes, pathways during early, intermediate, both hESFnonendo hESFendo, although blunted response observed latter. The normal involves tightly regulated cascade involving key components receptor MAPK that results inhibition E2-mediated proliferation eventual differentiation decidual phenotype, but this not established hESFendo P4. abnormal cell type may contribute compromised embryonic implantation infertility endometriosis.