Human Reproduction, Vol. 18, No. 9, 1767-1771,
September 2003
© 2003 European Society of Human Reproduction and Embryology
Effect of GnRH analogues on apoptosis and release of interleukin-1
and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis
1 Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, (C1428DNA) and 2 Instituto de Ginecología y Fertilidad (IFER), M.T. de Alvear 2259, (C1122AAI) Buenos Aires, Argentina
3 To whom correspondence should be addressed. e-mail: meresman{at}dna.uba.ar
BACKGROUND: The aim of the present study was to evaluate the effect of GnRH analogues on the in-vitro eutopic endometrial cell apoptosis and release of interleukin-1
(IL-1) and vascular endothelial growth factor (VEGF). METHODS: Biopsy specimens of eutopic endometrium obtained from 16 women with untreated endometriosis and 14 controls were studied. Apoptosis, IL-1 and VEGF release were evaluated in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA) as GnRH agonist, antide as GnRH antagonist, and a combination of both. The percentage of apoptotic cells was evaluated by the acridine orange–ethidium bromide technique, and IL-1 and VEGF concentrations were assessed by using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: We found that LA (100 ng/ml) enhanced apoptosis in endometrial cell cultures from endometriosis patients and controls and this effect was reversed by antide at 10–7 mol/l. IL-1 and VEGF release was downregulated by LA in cultures from controls and endometriosis patients. The addition of antide 10–7 mol/l reversed this inhibition. Endometrial cultures treated with antide at 10–7 mol/l did not show any significant effects compared with basal conditions. CONCLUSIONS: GnRH agonists appear to have a direct effect in endometrial cells cultures, by enhancing the percentage of apoptotic cells and decreasing the release of pro-mitogenic cytokines such as IL-1 and VEGF.
Key words: apoptosis/endometrial cell/endometriosis/GnRH agonist/IL-1/VEGF
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