Effect of a Vegf Inhibitory Treatment on The Folliculogenesis And Ovarian Apoptosis In Gonadotropin- Treated Prepuberal Rats

ABRAMOVICH DALHIA; PARBORELL FERNANDA; TESONE MARTA

Nebraska, USA

Congreso; 39th Annual Meeting of the Society for the Study of Reproduction; 2006

Angiogenesis is a process of vascular growth that is mainly limited to the reproductive system in healthy adult animals. VEGF is thought to play a key role in the regulation of angiogenesis in the ovary. This protein and its receptors VEGF-R1 and VEGF-R2 are expressed in granulosa and theca cells. The objective of this study was to determine the role of VEGF on the folliculogenesis and ovarian apoptosis. Female immature rats superovulated with eCG were injected with a VEGF inhibitor (Trap: soluble VEGF Receptor 1/Fc chimera in a dose of 0.1 or 0.5 mg/ovary) under the bursa of one ovary. The contralateral ovary was injected with vehicle (C). The ovaries were removed at different times for histological studies. Follicle growth was determined 12, 24 and 48 hours after surgery. The number of atretic follicles/ovary significantly increased after 48 h of Trap (0.5mg) treatment (C: 10.46±0.54; Trap: 16.38±1.27 %, p<0.05) whereas the number of periovulatory follicles/ovary significantly decreased (C: 14.08±1.49; Trap: 8.54±1.72 %, p <0.05). No significant changes were observed when 0.1 mg was injected. Trap treatment (0.5mg) significantly increased the number of apoptotic cells in antral follicles detected by the TUNEL technique 48 h after surgery (C: 3.17±0.82; Trap: 6.81±1.02 apoptotic cells/field, p<0,05). Antral follicles (250- 400 mm) were dissected under a stereoscopic microscope and used for Western blots. Trap injection reduced the ratio Bcl-xL/Bcl-xS and Bcl-2/Bax whereas the levels of Fas and Fas-L proteins did not change. Conclusions: The inhibition of VEGF activity would produce an increase in ovarian apoptosis, leading to a larger number of follicles to atresia. The mechanism could be through an increase blood vessel extension or a direct effect mediated by an ovarian VEGF receptor in granulosa/theca cells.