Sphingosine-1-phosphate restores endothelial barrier integrity in ovarian hyperstimulation syndrome

Autor: Flavia Saravia, I. de Zúñiga, M. Gomez Peña, Leopoldina Scotti, Griselda Irusta, Marta Tesone, Fernanda Parborell, Natalia Pascuali, Carlos Pomilio, M. Di Pietro, Dalhia Abramovich
Rok vydání: 2016
Předmět:
SPHINGOLIPIDS
0301 basic medicine
Embryology
Angiogenesis
Ovarian hyperstimulation syndrome
Vascular permeability
chemistry.chemical_compound
0302 clinical medicine
Sphingosine
ENDOTHELIO
Microscopy
Confocal
030219 obstetrics & reproductive medicine
Obstetrics and Gynecology
Patología
Medicina Básica
medicine.anatomical_structure
Female
Biología Reproductiva
CIENCIAS NATURALES Y EXACTAS
Adult
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD
Endothelium
Immunoblotting
Ovary
Biology
Cell Line
Ciencias Biológicas
Capillary Permeability
Ovarian Hyperstimulation Syndrome
03 medical and health sciences
Endothelial barrier
Internal medicine
Genetics
medicine
Humans
SPHONGOSINE 1P
Sphingosine-1-phosphate
Molecular Biology
Endothelial Cells
Cell Biology
medicine.disease
Sphingolipid
Follicular Fluid
030104 developmental biology
Endocrinology
Reproductive Medicine
chemistry
OHSS
Lysophospholipids
Developmental Biology
Zdroj: Molecular Human Reproduction.
ISSN: 1460-2407
1360-9947
DOI: 10.1093/molehr/gaw065
Popis: Are follicular fluid (FF) sphingosine-1-phosphate (S1P) levels in patients at risk of developing ovarian hyperstimulation syndrome (OHSS) altered and in part responsible for the high vascular permeability observed in these patients.FF S1P levels are lower in FF from patients at risk of OHSS and treatment with S1P may reduce vascular permeability in these patients.Although advances have been made in the diagnosis, and management of OHSS and in basic knowledge of its development, complete prevention has proven difficult.A total of 40 FF aspirates were collected from patients undergoing ART. The women (aged 25-39 years old) were classified into a control group (n = 20) or a group at risk of OHSS (n = 20). The EA.hy926 endothelial cell line was used to assess the efffects of FF from patients at risk of OHSS with or without the addition of S1P. An animal model that develops OHSS in immature Sprague-Dawley rats were also used.Migration assays, confocal microscopy analysis of actin filaments, immunoblotting and quail chorioallantoic membrane (CAM) assays of in-vivo angiogenesis were performed and statistical comparisons between groups were made.The S1P concentration was significantly lower in FF from patients at risk of OHSS (P = 0.03). The addition of S1P to this FF decreased cell migration (P0.05) and prevented VE-cadherin phosphorylation in endothelial cells (P0.05). S1P in the FF from patients at risk of OHSS increased the levels of VE-cadherin (P0.05), N-cadherin (P0.05) and β-catenin (P0.05), and partially reversed actin redistribution in endothelial cells. The addition of S1P in FF from patients at risk of OHSS also decreased the levels of vascular endothelial growth factor (VEGFN/A.The results of this study were generated from an in-vitro system. This model reflects the microvasculature in vivo. Even though the ideal model would be the use of human endothelial cells from the ovary, it is obviously not possible to carry out this kind of approach in ovaries of patients from ART. More studies will be necessary to delineate the effects of S1P in the pathogenesis of OHSS. Hence, clinical studies are needed in order to choose the most appropriate method of prevention and management.The use of bioactive sphingolipid metabolites may contribute to finding better and safer therapeutic strategies for the treatment of OHSS and other human diseases that display aberrant vascular leakage.This work was supported by grants ANPCyT (PICT 2012-897), CONICET (PIP 5471), Roemmers and Baron Foundation, Argentina. The authors declare no conflict of interest.
Databáze: OpenAIRE
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