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Abstract:

STUDY QUESTION: Can the bioactive lipid sphingosine-1 phosphate (SIP) act as an endothelial barrier-enhancing molecule and, in turn, restore the vascular integrity and homoeostasis in a rat model of ovarian hyperstimulation syndrome (OHSS). STUDY ANSWER: In vivo administration of SIP may prevent the early onset of OHSS and 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. SIP in follicular fluid from women at risk of developing OHSS are lower in comparison from women who are not at such risk and administration of SIP in an OHSS rat model decreases ovarian capillary permeability. STUDY DESIGN, SIZE, DURATION: We used an animal model that develops OHSS in immature Sprague-Dawley rats. The rats were randomly divided into three groups: The control group, which was injected with 10 IU of pregnant mare's serum gonadotropin (PMSG), and 10 IU of hCG 48 h later; the OHSS group, which was injected with excessive doses of PMSG (50 lU/day) for four consecutive days, followed by hCG; and the OHSS + SIP group, which was injected with the same doses of PMSG and hCG as the OHSS group and then treated with 5 pl SIP (I mM) under the bursa of both ovaries, whereas the other groups of animals received the SIP vehicle. 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 for hormone assays. One of the ovaries from each rat (n = 6) was used for Western immunoblot and the other for immunohistochemical analysis. Statistical comparisons between groups were carried out. MAIN RESULTS AND THE ROLE OF CHANCE: SIP administration reduced the ovarian weight (P < 0.05), and decreased the concentration of serum progesterone in the OHSS group compared to the OHSS group without treatment (P < 0.00I). The percentage of antral follicles in the OHSS group was lower than that in the control group. SIP increased the percentage of antral follicles (P < 0.05) and decreased the percentage of corpora lutea (P < 0.0I) and cystic structures in the OHSS group (P < 0.05). SIP had no effect on the expression levels of the enzymes 3p-hydroxysteroid dehydrogenase (3pHSD) or cholesterol side-chain cleavage enzyme (P450scc), but reduced the levels of steroidogenic acute regulatory protein (StAR) in OHSS rat ovaries (P < 0.05). SIP decreased the endothelial (P < 0.05) and periendothelial (P < 0.0I) cell area in OHSS rat ovaries. SIP restored the levels of N-cadherin and VE-cadherin proteins to control values. Furthermore, SI P enhanced the levels of claudin-5, occludin (P < 0.05) and sphingosine- 1-phosphate receptor 1 (SIPRI) in OHSS (P < 0.01). In addition, no histological differences were found in endometrium between OHSS and SI P-treated OHSS animals. LIMITATIONS REASONS FOR CAUTION: The results of this study were generated from an in vivo OHSS experimental model, which has been used by several authors and our group due to the similarity between the rat and human angiogenic systems. Further studies in patients will be needed to evaluate the effects of SIP in the pathogenesis of OHSS. WIDER IMPLICATIONS OF THE FINDINGS: These findings concern the pathophysiological importance of SIP in OHSS. More studies on the regulation of endothelial cell barrier function by SIP in reproductive pathological processes and its therapeutic application are required. LARGE SCALE DATA: N/A. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by grants from ANPCyT (PICT 20I2-897), CONICET (PIP 547I), Roemmers and Baron Foundations, Argentina. The authors declare no conflicts of interest. © 2017. Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Registro:

Documento: Artículo
Título:In vivo intrabursal administration of bioactive lipid sphingosine- 1-phosphate enhances vascular integrity in a rat model of ovarian hyperstimulation syndrome
Autor:Pietro, M.D.; Pascuali, N.; Scotti, L.; Irusta, G.; Bas, D.; May, M.; Tesone, M.; Abramovich, D.; Parborell, F.
Filiación:Instituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, Ciudad Autónoma de Buenos Aires, C1428ADN, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Intendente Güiraldes 2160, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina
Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Junin 954, Ciudad Autonoma de Buenos Aires, C1113AAD, Argentina
Palabras clave:Angiogenesis; OHSS; Ovary; Sphingolipids; Vascular integrity; 3(or 17)beta hydroxysteroid dehydrogenase; cholesterol monooxygenase (side chain cleaving); claudin 5; nectin 2; nerve cell adhesion molecule; occludin; progesterone; sphingosine 1 phosphate; sphingosine 1 phosphate receptor; steroidogenic acute regulatory protein; vascular endothelial cadherin; 3(or 17)beta hydroxysteroid dehydrogenase; cadherin; claudin 5; Cldn5 protein, rat; cytochrome P450; leukocyte antigen; lysophospholipid; N-cadherin, rat; nerve protein; occludin; Ocln protein, rat; phosphoprotein; progesterone; S1PR1 protein, rat; seric gonadotropin; sphingosine; sphingosine 1 phosphate receptor; sphingosine 1-phosphate; steroidogenic acute regulatory protein; vascular endothelial cadherin; angiogenesis; animal cell; animal experiment; animal model; animal tissue; antral follicle; Article; blood vessel permeability; controlled study; corpus luteum; drug effect; endometrium; female; immunohistochemistry; in vivo study; nonhuman; organ weight; ovary; ovary cyst; ovary follicle atresia; ovary hyperstimulation; pericyte; priority journal; progesterone blood level; protein expression; rat; rat model; smooth muscle cell; Sprague Dawley rat; steroidogenesis; Western blotting; analogs and derivatives; animal; blood; capillary permeability; disease model; drug effects; gene expression regulation; genetics; human; metabolism; organ size; ovary follicle; ovary hyperstimulation; pathology; pregnancy; 3-Hydroxysteroid Dehydrogenases; Animals; Antigens, CD; Cadherins; Capillary Permeability; Claudin-5; Corpus Luteum; Cytochrome P-450 Enzyme System; Disease Models, Animal; Female; Gene Expression Regulation; Gonadotropins, Equine; Humans; Lysophospholipids; Nerve Tissue Proteins; Occludin; Organ Size; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Phosphoproteins; Pregnancy; Progesterone; Rats; Rats, Sprague-Dawley; Receptors, Lysosphingolipid; Sphingosine
Año:2017
Volumen:23
Número:6
Página de inicio:417
Página de fin:427
DOI: http://dx.doi.org/10.1093/molehr/gax021
Título revista:Molecular Human Reproduction
Título revista abreviado:Mol. Hum. Reprod.
ISSN:13609947
CODEN:MHREF
CAS:3(or 17)beta hydroxysteroid dehydrogenase, 9015-81-0; cholesterol monooxygenase (side chain cleaving), 37292-81-2; occludin, 176304-61-3; progesterone, 57-83-0; sphingosine 1 phosphate, 26993-30-6; steroidogenic acute regulatory protein, 168183-61-7; cytochrome P450, 9035-51-2; seric gonadotropin, 9002-70-4; sphingosine, 123-78-4; 3-Hydroxysteroid Dehydrogenases; Antigens, CD; cadherin 5; Cadherins; Claudin-5; Cldn5 protein, rat; Cytochrome P-450 Enzyme System; Gonadotropins, Equine; Lysophospholipids; N-cadherin, rat; Nerve Tissue Proteins; Occludin; Ocln protein, rat; Phosphoproteins; Progesterone; Receptors, Lysosphingolipid; S1PR1 protein, rat; Sphingosine; sphingosine 1-phosphate; steroidogenic acute regulatory protein
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13609947_v23_n6_p417_Pietro

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Citas:

---------- APA ----------
Pietro, M.D., Pascuali, N., Scotti, L., Irusta, G., Bas, D., May, M., Tesone, M.,..., Parborell, F. (2017) . In vivo intrabursal administration of bioactive lipid sphingosine- 1-phosphate enhances vascular integrity in a rat model of ovarian hyperstimulation syndrome. Molecular Human Reproduction, 23(6), 417-427.
http://dx.doi.org/10.1093/molehr/gax021
---------- CHICAGO ----------
Pietro, M.D., Pascuali, N., Scotti, L., Irusta, G., Bas, D., May, M., et al. "In vivo intrabursal administration of bioactive lipid sphingosine- 1-phosphate enhances vascular integrity in a rat model of ovarian hyperstimulation syndrome" . Molecular Human Reproduction 23, no. 6 (2017) : 417-427.
http://dx.doi.org/10.1093/molehr/gax021
---------- MLA ----------
Pietro, M.D., Pascuali, N., Scotti, L., Irusta, G., Bas, D., May, M., et al. "In vivo intrabursal administration of bioactive lipid sphingosine- 1-phosphate enhances vascular integrity in a rat model of ovarian hyperstimulation syndrome" . Molecular Human Reproduction, vol. 23, no. 6, 2017, pp. 417-427.
http://dx.doi.org/10.1093/molehr/gax021
---------- VANCOUVER ----------
Pietro, M.D., Pascuali, N., Scotti, L., Irusta, G., Bas, D., May, M., et al. In vivo intrabursal administration of bioactive lipid sphingosine- 1-phosphate enhances vascular integrity in a rat model of ovarian hyperstimulation syndrome. Mol. Hum. Reprod. 2017;23(6):417-427.
http://dx.doi.org/10.1093/molehr/gax021