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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 BCL2L1L:BCL2L1s 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. © 2006 by the Society for the Study of Reproduction, Inc.

Registro:

Documento: Artículo
Título:Effect of a vascular endothelial growth factor (VEGF) inhibitory treatment on the folliculogenesis and ovarian apoptosis in gonadotropin-treated prepubertal rats
Autor:Abramovich, D.; Parborell, F.; Tesone, M.
Filiación:Instituto de Biología y Medicina Experimental (IByME)-CONICET, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Palabras clave:Angiogenesis; Apoptosis; Female reproductive tract; Follicular development; Growth factors; Ovary; Vascular endothelial growth factor A; apoptosis inducing factor; apoptosis inhibitor; chimeric protein; chorionic gonadotropin; DNA fragment; Fas antigen; FAS ligand; Fc receptor; gonadotropin; ligand; novormon; protein Bax; protein bcl 2; protein bcl2l1; protein trap; unclassified drug; vasculotropin A; vasculotropin inhibitor; vasculotropin receptor 1; animal experiment; animal tissue; apoptosis; article; cell count; cell survival; chimera; controlled study; DNA isolation; down regulation; drug mechanism; early antral follicle; female; gene overexpression; nick end labeling; nonhuman; ovary follicle; ovary follicle atresia; ovary follicle development; ovulation; periovulatory follicle; preantral follicle; prepuberty; priority journal; protein expression; protein family; protein function; quantitative analysis; rat; tissue section; upregulation; Animals; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Chorionic Gonadotropin; DNA; DNA Fragmentation; Electrophoresis, Agar Gel; Fas Ligand Protein; Fas-Associated Death Domain Protein; Female; Genes, bcl-1; Genes, bcl-2; In Situ Nick-End Labeling; Ovarian Follicle; Ovary; Rats; Rats, Sprague-Dawley; Sexual Maturation; Vascular Endothelial Growth Factor A
Año:2006
Volumen:75
Número:3
Página de inicio:434
Página de fin:441
DOI: http://dx.doi.org/10.1095/biolreprod.106.051052
Título revista:Biology of Reproduction
Título revista abreviado:Biol. Reprod.
ISSN:00063363
CODEN:BIREB
CAS:chorionic gonadotropin, 9002-61-3; gonadotropin, 63231-54-9; protein bcl 2, 219306-68-0; vasculotropin A, 489395-96-2; bcl-2-Associated X Protein; Chorionic Gonadotropin; DNA, 9007-49-2; Fas Ligand Protein; Fas-Associated Death Domain Protein; Vascular Endothelial Growth Factor A
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063363_v75_n3_p434_Abramovich

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Citas:

---------- APA ----------
Abramovich, D., Parborell, F. & Tesone, M. (2006) . Effect of a vascular endothelial growth factor (VEGF) inhibitory treatment on the folliculogenesis and ovarian apoptosis in gonadotropin-treated prepubertal rats. Biology of Reproduction, 75(3), 434-441.
http://dx.doi.org/10.1095/biolreprod.106.051052
---------- CHICAGO ----------
Abramovich, D., Parborell, F., Tesone, M. "Effect of a vascular endothelial growth factor (VEGF) inhibitory treatment on the folliculogenesis and ovarian apoptosis in gonadotropin-treated prepubertal rats" . Biology of Reproduction 75, no. 3 (2006) : 434-441.
http://dx.doi.org/10.1095/biolreprod.106.051052
---------- MLA ----------
Abramovich, D., Parborell, F., Tesone, M. "Effect of a vascular endothelial growth factor (VEGF) inhibitory treatment on the folliculogenesis and ovarian apoptosis in gonadotropin-treated prepubertal rats" . Biology of Reproduction, vol. 75, no. 3, 2006, pp. 434-441.
http://dx.doi.org/10.1095/biolreprod.106.051052
---------- VANCOUVER ----------
Abramovich, D., Parborell, F., Tesone, M. Effect of a vascular endothelial growth factor (VEGF) inhibitory treatment on the folliculogenesis and ovarian apoptosis in gonadotropin-treated prepubertal rats. Biol. Reprod. 2006;75(3):434-441.
http://dx.doi.org/10.1095/biolreprod.106.051052