IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Meloxicam decreases ovarian hyperstimulation syndrome in arat model.
Autor/es:
QINTANA R; KOPCOW L.; DIRADOURIAN M.; MARCONI G.; SOIZA RELLY M.; YOUNG E.; PAZ D.A.
Lugar:
Praga, República Checa
Reunión:
Congreso; 22nd Annual Meeting of The European Society of Human Reproduction and Embryology; 2006
Institución organizadora:
European Society of Human Reproduction and Embryology
Resumen:
Introduction: Ovarian hyperstimulation syndrome (OHSS) is a complication of ovulation induction. Vascular endothelial growth factor (VEGF) has been considered as a prime causative factor of OHSS progression. A relationship between the enzyme cyclooxygenase-2 (COX-2) and production of VEGF has been demonstrated in colon and prostate cancer. In the present study we evaluated the effects of Meloxicam (a COX-2 inhibitor) on OHSS induced rats and compared the results with OHSS induced rats without meloxicam treatment and with ovulation-induced rats and control group.  Materials and Methods: Eighty 22 days old  female Wistar rats were divided in four groups. Group 1 (control group) (n = 20) received 0.1 ml of i.p. saline from day 22 to day 26. Group 2 (mild-stimulated group) (n = 20) received 10 IU of PMSG on day 24 and 10 IU of hCG 48 hs later (day 26). Group 3 (OHSS group) (n = 20) was given 10 IU of PMSG for four consecutive days from day 22 and 30 IU hCG on the fifth day in order to induce OHSS. Group 4 was treated in same way as Group 3 but receiving 2 ul of meloxicam 2 hours before the PMSG injection, for 4 consecutive days, and 2 hours before the hCG injection on the fifth day. The VEGF expression was evaluated by 2 methods: semiquantitative immunohistochemistry using a avidin-biotin peroxidase complex on paraffin sections and western blotting from ovaries homogenates. In both cases we used an specific antibody to VEGF.  The number of follicles was evaluated on hematoxilin and eosin sections. Results:  Hyperstimulation treatment produces a significative increase in the ovarian weight when compared with control animals. There are no differences in the ovary weight between group 1 and 2 after 6 days of treatment (Group1: 140 mg  +  1.8; Group 2: 190 mg + 1.4) The OHSS group showed a significantly (p<0.001) increase in the ovarian weight in relation to control group and mild-stimulated group.This higher weight in the OHSS group was reverted by meloxicam after 6 days of treatment ( Group 3: 385 mg  +  19.6 and Group 4: 235 mg  +  6.9, p<0.001). The number of antral follicles was no different in the four treated groups but a tendency to a reduction in the number of antral follicles was observed in group 4 (OHSS and meloxicam treated) when compared with the group 3 (OHSS). The follicle number were group 2: 19,8 + 2.1; Group 3: 41 +  7 and Group 4: 35,4 + 11.4. VEGF immunoreactivity (VEGF-ir) was observed in the theca and stroma cells, with a weakly staining in the granulosa cells of the control group. In the mild-stimulated and OHSS groups, the granulosa cells of preovulatory follicles showed a strong immunoreactivity with a significative increase in the ovaries from the OHSS group. The ovaries from meloxicam treated group showed a more lightly immunoreactivity than the OHSS group (H-SCORE values were: Group 1:  1,77  +  0,34; Group 2: 4,05  + 0,42; Group 3: 7,2  +  1,44 and Group 4: 4,7  +  0,52). The western blot showed similar results with a significative difference between hyperstimulated and hyperstimulated + meloxicam ovaries (p<0.001) the values (expressed in arbitrary units corrected to the actin concentration) were: Group 3 (OHSS): 6.56 + 1.97 Group 4 (OHSS + Meloxicam): 11.17 + 1.28. Serum estradiol levels in hyperstimulated rats showed an increase approximately 10 times when compared with control group. The meloxicam treatment was ineffective in reverting the estrogenic rice in OHSS rats.  Conclutions: Our results in a rat model are suggesting that meloxicam may have beneficial effects on OHSS reducing the ovarian weight and VEGF expression.