endometriosis stromal cell with estrogen

Objective : To compare transcriptomes induced by the estrogen components of combined oral contraceptives, estetrol (E4), and ethynylestradiol (EE), and estradiol (E2) in human primary endometriotic stromal cells (ESCs). Design: ESCs were cultured in the presence of E4 (10-6 mol/L), E2 (10-8 mol/L) or EE (10-9 mol/L) for 24 hours. The transcriptomes induced by E4 were compared with those by E2 and EE. Subjects: ESCs were obtained from patients with ovarian endometriomas. Main Outcome Measures: Comprehensive transcriptomes were examined using RNA sequencing analysis. mRNA levels were measured using reverse transcription and quantitative polymerase chain reaction (RT-qPCR) analysis. Results: E4 treatment resulted in 114 differentially expressed genes compared to the control (|log2fold change| >0.2). Within these genes, 79% (90 genes) changed in the same manner as with EE and E2. Of these genes, the expression levels of GREB1, PGR and BMP6 were validated using RT-qPCR analysis. In contrast, 21% (24 genes) changed in E4-preferential manner. Of these genes, FAM72A and ENSG00000280800 were validated using RT-qPCR analysis. Conclusion: Our results showed that the effect of E4 on ESC gene expression generally similar to those caused by EE and E2 but differed for some genes. This study will advance our understanding of combined oral contraceptives that have practical importance for the treatment of endometriosis.