Fertility and Sterility
Volume 93, Issue 1 , Pages 239-250, 1 January 2010

Gene therapy targeting leiomyoma: adenovirus-mediated delivery of dominant-negative estrogen receptor gene shrinks uterine tumors in Eker rat model

  • Memy H. Hassan, M.Sc.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
    • Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
    • ,
  • Salama A. Salama, Ph.D.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
    • ,
  • Dong Zhang, Ph.D.

      Affiliations

    • Department of Carcinogenesis, M. D. Anderson Cancer Center, University of Texas, Texas
    • Center for Women Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, Tennessee
    • ,
  • Hossam M.M. Arafa, Ph.D.

      Affiliations

    • Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
    • ,
  • Farid M.A. Hamada, Ph.D.

      Affiliations

    • Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
    • ,
  • Hala Fouad, M.D., Ph.D.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
    • ,
  • Cheryl C. Walker, Ph.D.

      Affiliations

    • Department of Carcinogenesis, M. D. Anderson Cancer Center, University of Texas, Texas
    • ,
  • Ayman Al-Hendy, M.D., Ph.D.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
    • Center for Women Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, Tennessee
    • Corresponding Author InformationReprint requests: Ayman Al-Hendy, Professor and Vice Chair, Center for Women Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, 1005 Dr. D. B. Todd Jr. Blvd., Nashville, Tennessee 37208 (FAX: 615-963-3125).

Received 6 September 2008; received in revised form 23 September 2008; accepted 30 September 2008. published online 14 January 2009.

Objective

To evaluate the utility of gene therapy for uterine fibroids in the Eker rat model using an adenovirus-mediated delivery of a dominant-negative estrogen receptor gene (Ad-DNER).

Design

Animal study.

Setting

University animal laboratory.

Animal(s)

Twenty-seven female Eker rats.

Intervention(s)

We randomized Eker rats with magnetic resonance imaging (MRI)–confirmed uterine leiomyomas to a single treatment of direct intrafibroid injection with Ad-DNER, Ad–bacterial ß-galactosidase, or vehicle.

Main Outcome Measure(s)

Tumor volumes were determined by MRI scanning and caliper measurement. Samples of serum, fibroid tumors, and various organs were collected at 8, 15, and 30 days after treatment to assess treatment safety and efficacy.

Result(s)

The Ad-DNER treatment significantly decreased uterine fibroid volume by 45%, 80%, and 77.4% of pretreatment volume at days 8, 15, and 30, respectively, and modulated the expression of apoptosis-, proliferation-, and extracellular matrix–related genes' compared with control animals. The Ad-DNER did not produce any toxic effects in nontarget tissues.

Conclusion(s)

The Ad-DNER treatment shrinks Eker rats' fibroids, in part, via modulation of several estrogen-regulated genes. This safe gene therapy approach presents a promising conservative treatment option for women with symptomatic uterine fibroids.

Key Words: Uterine leiomyoma, gene therapy, dominant-negative estrogen receptor

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 M.H. has nothing to disclose. S.S. has nothing to disclose. D.Z. has nothing to disclose. H.A. has nothing to disclose. F.H. has nothing to disclose. H.F. has nothing to disclose. C.W. has nothing to disclose. A.A.-H. has nothing to disclose.

 Supported by National Institutes of Health/National Institute of Child Health and Human Development grant no. R01 HD046228-01.

PII: S0015-0282(08)04127-7

doi:10.1016/j.fertnstert.2008.09.086

Fertility and Sterility
Volume 93, Issue 1 , Pages 239-250, 1 January 2010

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