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This Article Full Text Full Text (PDF) All Versions of this Article: 75/3/434    most recent biolreprod.106.051052v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abramovich, D. Articles by Tesone, M. Search for Related Content PubMed PubMed Citation Articles by Abramovich, D. Articles by Tesone, M. Agricola Articles by Abramovich, D. Articles by Tesone, M.

Effect of a Vascular Endothelial Growth Factor (VEGF) Inhibitory Treatment on the Folliculogenesis and Ovarian Apoptosis in Gonadotropin-Treated Prepubertal Rats¹

Instituto de Biología y Medicina Experimental (IByME)—CONICET,³ Departamento de Química Biológica,⁴ Facultad de Ciencias Exactas, Universidad de Buenos Aires, Buenos Aires 1428, Argentina

ABSTRACT

In the present study, we investigated whether vascular endothelial growth factor A (VEGFA) plays a critical intraovarian survival role in gonadotropin-dependent folliculogenesis. The effect of an intrabursal administration of a VEGFA antagonist on follicular development, apoptosis, and levels of pro- and antiapoptotic proteins of BCL2 family members (BAX, BCL2, and BCL2L1), as well as of TNFRSF6 (also known as FAS) and FAS ligand (FASLG), was examined. To inhibit VEGFA, a soluble FLT1/Fc Chimera (Trap) was administered to prepubertal eCG-treated rats. Injection of 0.5 µg of Trap per ovary did not change the number of preantral follicles (PFs) or early antral follicles (EAFs); however, it significantly decreased the number of periovulatory follicles 48 h after surgery and significantly increased the number of atretic follicles. No significant differences were found in any stage of the follicles either 12 or 24 h after injection. Cells undergoing DNA fragmentation were quantified by performing TUNEL on ovarian sections. Trap treatment caused a twofold increase in the number of apoptotic cells in EAFs. DNA isolated from antral follicles incubated for 24 h exhibited the typical apoptotic DNA pattern. Follicles obtained from Trap-treated ovaries showed a significant increase in the spontaneous onset of apoptotic DNA fragmentation. The injection of Trap significantly increased the levels of BAX and decreased the levels of BCL2 protein. The ratio of BCL2L1_L:BCL2L1_s was significantly diminished in follicles obtained from ovaries treated with Trap. No changes in the levels of TNFRSF6 or FASLG were observed after treatment. We concluded that the local inhibition of VEGFA activity appears to produce an increase in ovarian apoptosis through an imbalance among the BCL2 family members, thus leading a larger number of follicles to atresia.

angiogenesis, apoptosis, female reproductive tract, follicular development, growth factors, ovary, vascular endothelial growth factor A

¹ Supported by the Agencia Nacional de Promoción Científica y Tecnológica (BID 1201 OC-AR PICT 99:05–06384) and the Universidad de Buenos Aires (X237).

² Correspondence. FAX: 54 011 4786 2564; mtesone{at}dna.uba.ar

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