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

Essam Eldin R. Othman, Salama Salama, Nahed Ismail, Ayman Al-Hendy

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)462-471
Number of pages10
JournalFertility and sterility
Volume88
Issue number2
DOIs
StatePublished - Aug 1 2007

Fingerprint

Endometriosis
Adenoviridae
Estrogen Receptors
Genetic Therapy
Cell Proliferation
Apoptosis
Cytokines
Genes
Outcome Assessment (Health Care)
Uterine Prolapse
Enterovirus
Chemokine CCL2
Leiomyoma
Vascular Endothelial Growth Factor A
Transfection
Interleukin-6
Estrogens
Cell Death
Research Design
Cell Count

Keywords

  • Endometriosis
  • adenovirus
  • dominant negative
  • gene therapy

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

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. / Othman, Essam Eldin R.; Salama, Salama; Ismail, Nahed; Al-Hendy, Ayman.

In: Fertility and sterility, Vol. 88, No. 2, 01.08.2007, p. 462-471.

Research output: Contribution to journalArticle

@article{928d793eea1b40b3af34ee6763dfc9cf,
title = "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",
abstract = "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.",
keywords = "Endometriosis, adenovirus, dominant negative, gene therapy",
author = "Othman, {Essam Eldin R.} and Salama Salama and Nahed Ismail and Ayman Al-Hendy",
year = "2007",
month = "8",
day = "1",
doi = "10.1016/j.fertnstert.2006.11.046",
language = "English (US)",
volume = "88",
pages = "462--471",
journal = "Fertility and Sterility",
issn = "0015-0282",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Toward gene therapy of endometriosis

T2 - adenovirus-mediated delivery of dominant negative estrogen receptor genes inhibits cell proliferation, reduces cytokine production, and induces apoptosis of endometriotic cells

AU - Othman, Essam Eldin R.

AU - Salama, Salama

AU - Ismail, Nahed

AU - Al-Hendy, Ayman

PY - 2007/8/1

Y1 - 2007/8/1

N2 - 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.

AB - 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.

KW - Endometriosis

KW - adenovirus

KW - dominant negative

KW - gene therapy

UR - http://www.scopus.com/inward/record.url?scp=34547690893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547690893&partnerID=8YFLogxK

U2 - 10.1016/j.fertnstert.2006.11.046

DO - 10.1016/j.fertnstert.2006.11.046

M3 - Article

VL - 88

SP - 462

EP - 471

JO - Fertility and Sterility

JF - Fertility and Sterility

SN - 0015-0282

IS - 2

ER -