Toward gene therapy of endometriosis: adenovirus-mediated delivery of dominant negative estrogen receptor genes inhibits cell proliferation, reduces cytokine production, and induces apoptosis of endometriotic cells

OBJECTIVE: To use dominant negative mutants of estrogen receptor genes delivered to endometriosis cells via an adenovirus vector (Ad-DN-ER) to abrogate estrogen action on these cells. DESIGN: Experimental in vitro study. SETTING: University research laboratory. PATIENT(S): Patients with ovarian endometriomas provided endometriotic cells, and patients with uterine prolapse or subserous leiomyoma provided control endometrial cells. INTERVENTION(S): Transfection of endometriotic cells by dominant negative estrogen receptor genes via adenovirus vector (Ad-DN-ER). MAIN OUTCOME MEASURE(S): The main outcome measures were cellular proliferation, cytokine production, and induction of apoptosis in endometriotic cells. RESULT(S): Coxsackievirus-adenovirus receptor mRNA expression and adenovirus transduction efficiency were significantly higher in endometriotic than normal endometrial cells. Ad-DN-ER-treated endometriotic cells, as compared with control virus-treated cells, showed cell rounding and detachment (cell death), a 72% reduction in the number of viable cells 5 days after transduction, significantly less production of monocyte chemotactic protein-1 (7.8 +/- 0.5 vs. 152.8 +/- 1.9 pg/mL, respectively), vascular endothelial growth factor (356.2 +/- 11.6 vs. 997.3 +/- 16.5 pg/mL, respectively), and interleukin-6 (268.7 +/- 2.6 vs. 414.5 +/- 3.6 pg/mL, respectively), and a significantly higher percentage of apoptotic cells (51.2 +/- 7.8 vs. 23.8 +/- 1.7, respectively). CONCLUSION(S): An adenovirus can effectively transfect endometriotic cells in vitro. The DN-ER delivered to endometriotic cells via an adenovirus decreases cell proliferation, induces apoptosis, and decreases cytokine production. Adenovirus-mediated gene therapy may represent a potential therapeutic option for endometriosis in the future.