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.


METHODS
Experimental in vitro study.


METHODS
University research laboratory.


METHODS
Patients with ovarian endometriomas provided endometriotic cells, and patients with uterine prolapse or subserous leiomyoma provided control endometrial cells.


METHODS
Transfection of endometriotic cells by dominant negative estrogen receptor genes via adenovirus vector (Ad-DN-ER).


METHODS
The main outcome measures were cellular proliferation, cytokine production, and induction of apoptosis in endometriotic cells.


RESULTS
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).


CONCLUSIONS
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.
Othman
Essam-Eldin R
EE
Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt.
Salama
Salama
S
Ismail
Nahed
N
Al-Hendy
Ayman
A
D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016207:Cytokines / Q000096:biosynthesis*; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology; D006801:Humans; D050505:Mutant Proteins / Q000502:physiology; D011960:Receptors, Estrogen / Q000235:genetics* / Q000502:physiology*; D011991:Receptors, Virus / Q000235:genetics; D014162:Transfection
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016207:Cytokines; D050505:Mutant Proteins; D011960:Receptors, Estrogen; D011991:Receptors, Virus