Local VEGF inhibition prevents ovarian alterations associated with ovarian hyperstimulation syndrome

Leopoldina Scotti; Dalhia Abramovich; Natalia Pascuali; Griselda Irusta; Gabriela Meresman; Marta Tesone; Fernanda Parborell

doi:10.1016/j.jsbmb.2014.08.013

Local VEGF inhibition prevents ovarian alterations associated with ovarian hyperstimulation syndrome

J Steroid Biochem Mol Biol. 2014 Oct:144 Pt B:392-401. doi: 10.1016/j.jsbmb.2014.08.013. Epub 2014 Aug 23.

Authors

Leopoldina Scotti¹, Dalhia Abramovich¹, Natalia Pascuali¹, Griselda Irusta¹, Gabriela Meresman¹, Marta Tesone², Fernanda Parborell³

Affiliations

¹ Instituto de Biología y Medicina Experimental (IByME) - CONICET, Buenos Aires, Argentina.
² Instituto de Biología y Medicina Experimental (IByME) - CONICET, Buenos Aires, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
³ Instituto de Biología y Medicina Experimental (IByME) - CONICET, Buenos Aires, Argentina. Electronic address: [email protected].

PMID: 25151950
DOI: 10.1016/j.jsbmb.2014.08.013

Abstract

The relationship between human chorionic gonadotropin and ovarian hyperstimulation syndrome (OHSS) is partially mediated by vascular endothelial growth factor A (VEGF). The aim of this study was to investigate the effects of VEGF inhibition on the development of corpora lutea (CL) and cystic structures, steroidogenesis, apoptosis, cell proliferation, endothelial cell area, VEGF receptors (KDR and Flt-1), claudin-5 and occludin levels in ovaries from an OHSS rat model. The VEGF inhibitor used (VEGF receptor-1 (FLT-1)/Fc chimera, TRAP) decreased the concentrations of progesterone and estradiol as well as the percentage of CL and cystic structures in OHSS rats, and increased apoptosis in CL. Endothelial cell area in CL and KDR expression and its phosphorylation were increased, whereas claudin-5 and occludin levels were decreased in the OHSS compared to the control TRAP reversed these parameters. Our findings indicate that VEGF inhibition prevents the early onset of OHSS and decreases its severity in rats.

Keywords: Angiogenesis; Apoptosis; Cell proliferation; OHSS; Ovary; VEGF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / pharmacology*
Animals
Apoptosis / drug effects
Cell Proliferation / drug effects
Claudin-5 / metabolism
Endothelial Cells / drug effects
Endothelial Cells / metabolism
Estradiol / blood
Female
Occludin / metabolism
Ovarian Hyperstimulation Syndrome / metabolism*
Ovarian Hyperstimulation Syndrome / pathology
Ovary / drug effects
Ovary / metabolism
Ovary / pathology
Progesterone / blood
Rats, Sprague-Dawley
Receptors, Vascular Endothelial Growth Factor / pharmacology*
Recombinant Fusion Proteins / pharmacology*
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-1 / metabolism
Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

Angiogenesis Inhibitors
Claudin-5
Cldn5 protein, rat
Occludin
Ocln protein, rat
Recombinant Fusion Proteins
Vascular Endothelial Growth Factor A
vascular endothelial growth factor A, rat
aflibercept
Progesterone
Estradiol
Flt1 protein, rat
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2