IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
In vivo intrabursal administration of bioactive lipid sphingosine-1-phosphate enhances vascular integrity in a rat model of ovarian hyperstimulation syndrome
Autor/es:
PARBORELL F; MAY M; SCOTTI L; ABRAMOVICH D; BAS D; PASCUALI N; TESONE M; IRUSTA G; DI PIETRO M
Revista:
MOLECULAR HUMAN REPRODUCTION.
Editorial:
OXFORD UNIV PRESS
Referencias:
Año: 2017 p. 1 - 11
ISSN:
1360-9947
Resumen:
STUDY QUESTION: Can the bioactive lipid sphingosine-1 phosphate (S1P) act as anendothelial barrier-enhancing molecule and, in turn, restore the vascularintegrity and homoeostasis in a rat model of ovarian hyperstimulation syndrome(OHSS).STUDY ANSWER: In vivo administration of S1P may prevent the early onset of OHSSand decrease its severity.WHAT IS KNOWN ALREADY: Although advances in the prediction and treatment of OHSS have been made, complete prevention has not been possible yet. S1P in follicular fluid from women at risk of developing OHSS are lower in comparison from womenwho are not at such risk and administration of S1P in an OHSS rat model decreasesovarian capillary permeability.STUDY DESIGN, SIZE, DURATION: We used an animal model that develops OHSS inimmature Sprague-Dawley rats. The rats were randomly divided into three groups:the control group, which was injected with 10 IU of pregnant mare´s serumgonadotropin (PMSG), and 10 IU of hCG 48 h later; the OHSS group, which wasinjected with excessive doses of PMSG (50 IU/day) for four consecutive days,followed by hCG; and the OHSS + S1P group, which was injected with the same dosesof PMSG and hCG as the OHSS group and then treated with 5 μl S1P (1 mM) under thebursa of both ovaries, whereas the other groups of animals received the S1Pvehicle.PARTICIPANTS /MATERIALS, SETTING, METHODS: Rats were killed by decapitation 48 h after the hCG injection for ovary, endometrium and blood collection. The ovaries were weighed and then used for subsequent assays, while the serum was used forhormone assays. One of the ovaries from each rat (n = 6) was used for Westernimmunoblot and the other for immunohistochemical analysis. Statisticalcomparisons between groups were carried out.MAIN RESULTS AND THE ROLE OF CHANCE: S1P administration reduced the ovarianweight (P < 0.05), and decreased the concentration of serum progesterone in theOHSS group compared to the OHSS group without treatment (P < 0.001). Thepercentage of antral follicles in the OHSS group was lower than that in thecontrol group. S1P increased the percentage of antral follicles (P < 0.05) anddecreased the percentage of corpora lutea (P < 0.01) and cystic structures in theOHSS group (P < 0.05). S1P had no effect on the expression levels of the enzymes 3β-hydroxysteroid dehydrogenase (3βHSD) or cholesterol side-chain cleavage enzyme(P450scc), but reduced the levels of steroidogenic acute regulatory protein(StAR) in OHSS rat ovaries (P < 0.05). S1P decreased the endothelial (P < 0.05)and periendothelial (P < 0.01) cell area in OHSS rat ovaries. S1P restored thelevels of N-cadherin and VE-cadherin proteins to control values. Furthermore, S1Penhanced the levels of claudin-5, occludin (P < 0.05) and sphingosine-1-phosphatereceptor 1 (S1PR1) in OHSS (P < 0.01). In addition, no histological differenceswere found in endometrium between OHSS and S1P-treated OHSS animals.LIMITATIONS REASONS FOR CAUTION: The results of this study were generated from anin vivo OHSS experimental model, which has been used by several authors and ourgroup due to the similarity between the rat and human angiogenic systems. Furtherstudies in patients will be needed to evaluate the effects of S1P in thepathogenesis of OHSS.WIDER IMPLICATIONS OF THE FINDINGS: These findings concern the pathophysiologicalimportance of S1P in OHSS. More studies on the regulation of endothelial cellbarrier function by S1P in reproductive pathological processes and itstherapeutic application are required.LARGE SCALE DATA: N/A.STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by grants fromANPCyT (PICT 2012-897), CONICET (PIP 5471), Roemmers and Baron Foundations,Argentina. The authors declare no conflicts of interest.DOI: 10.1093/molehr/gax021 PMID: 28379469