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Reproductive Sciences, Vol. 14, No. 8, 825-835 (2007)
DOI: 10.1177/1933719107305865

The Broad-Spectrum Chemokine Inhibitor NR58-3.14.3 Suppresses the Implantation and Survival of Human Endometrial Implants in the Nude Mice Endometriosis Model

Umit A. Kayisli, PhD

Department of Obstetrics, Gynecology and Reproductive Sciences Yale University School of Medicine, New Haven, Connecticut

Murat Berkkanoglu, MD

Department of Obstetrics, Gynecology and Reproductive Sciences Yale University School of Medicine, New Haven, Connecticut

Lufang Zhang, MD

Department of Obstetrics, Gynecology and Reproductive Sciences Yale University School of Medicine, New Haven, Connecticut

Gulnur Kizilay, PhD

Department of Histology and Embryology Trakya University, Edirne, Turkey

Aydin Arici, MD

Department of Obstetrics, Gynecology and Reproductive Sciences Yale University School of Medicine, New Haven, Connecticut, aydin.arici{at}yale.edu

Many chemokines likely contribute to the pathogenesis of endometriosis. The authors hypothesize that the broad-spectrum chemokine inhibitor NR58-3.14.3 may prevent ectopic human endometrium implantation and growth. After placing human endometrium fragments into the peritoneal cavity, ovariectomized athymic nude mice (n = 31) receiving intramuscular estradiol valerate were randomly assigned to daily intraperitoneal injections of either phosphate-buffered saline or NR58-3.14.3. Fourteen days later, the implant number and volume, proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase (TdT)—mediated dUTP nick end-labeling (TUNEL) index, and MTT cell viability were assessed in the implants. NR58-3.14.3 reduced the total number (45%) and total volume (81%) of endometriotic lesions (P < .05) and revealed a lower PCNA and higher TUNEL index in ectopic implants compared with controls (P < .05). NR58-3.14.3 treatment did not affect endometrial cell proliferation in vitro. NR58-3.14.3, by possibly regulating cell survival, can reduce the number and size of ectopic implants in vivo, supporting the potential use of chemokine inhibitors in novel therapies for endometriosis.

Key Words: Endometriosis • chemokine inhibitors • proliferation • apoptosis • nude mice.


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