Gonadotropin-releasing hormone agonist (GnRH-a) induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis

MERESMAN GF; BILOTAS M; BUQUET RA; BARAÑAO RI; SUELDO C; TESONE M

FERTILITY AND STERILITY

Año: 2003 p. 702 - 707

0015-0282

Objective: There is a growing evidence that suggest a direct action of GnRH-a on endometrial growth. Consequently, our purpose was to evaluate the effect of GnRH-a on the in-vitro eutopic endometrial cell growth and apoptosis. Design: Prospective study. Setting: Research institute and clinical fertility center. Patients: Sixteen women with untreated endometriosis and 14 controls. Interventions: Biopsy specimens of eutopic endometrium were obtained from all subjects. Apoptosis and cell proliferation were examined in epithelial endometrial cell cultures after incubation with Leuprolide acetate (LA), Antide, and a combination of both. Main outcome measure(s): Percentage of apoptotic cells was evaluated by the acridine orange - ethidium bromide technique; cell proliferation was assessed by 3H-thymidine incorporation. Results: LA (100 ng/ml) enhanced apoptosis in endometrial cultures from endometriosis patients and controls and this effect was reversed by Antide 10-7M. Cell proliferation was down-regulated by LA at 1 ng/ml, 10 ng/ml and 100 ng/ml in cultures from non-endometriosis women and endometriosis patients. The addition of Antide 10-7 M reversed this inhibition. Conclusions: GnRH-a appears to have a direct effect, by enhancing the apoptotic index and decreasing the cell proliferation in endometrial cells. Key words: GnRH agonist, endometriosis, endometrial epithelial cells, apoptosis, cell proliferation.