PMID- 28379469 OWN - NLM STAT- MEDLINE DCOM- 20180313 LR - 20191210 IS - 1460-2407 (Electronic) IS - 1360-9947 (Linking) VI - 23 IP - 6 DP - 2017 Jun 1 TI - In vivo intrabursal administration of bioactive lipid sphingosine-1-phosphate enhances vascular integrity in a rat model of ovarian hyperstimulation syndrome. PG - 417-427 LID - 10.1093/molehr/gax021 [doi] AB - STUDY QUESTION: Can the bioactive lipid sphingosine-1 phosphate (S1P) 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 S1P 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. S1P 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 S1P 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 IU/day) for four consecutive days, followed by hCG; and the OHSS + S1P group, which was injected with the same doses of PMSG and hCG as the OHSS group and then treated with 5 mul S1P (1 mM) under the bursa of both ovaries, whereas the other groups of animals received the S1P 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: S1P 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 < 0.001). The percentage of antral follicles in the OHSS group was lower than that in the control group. S1P increased the percentage of antral follicles (P < 0.05) and decreased the percentage of corpora lutea (P < 0.01) and cystic structures in the OHSS group (P < 0.05). S1P had no effect on the expression levels of the enzymes 3beta-hydroxysteroid dehydrogenase (3betaHSD) 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 the levels of N-cadherin and VE-cadherin proteins to control values. Furthermore, S1P enhanced the levels of claudin-5, occludin (P < 0.05) and sphingosine-1-phosphate receptor 1 (S1PR1) in OHSS (P < 0.01). In addition, no histological differences were found in endometrium between OHSS and S1P-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 S1P in the pathogenesis of OHSS. WIDER IMPLICATIONS OF THE FINDINGS: These findings concern the pathophysiological importance of S1P in OHSS. More studies on the regulation of endothelial cell barrier function by S1P 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 2012-897), CONICET (PIP 5471), Roemmers and Baron Foundations, Argentina. The authors declare no conflicts of interest. CI - (c) The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Di Pietro, Mariana AU - Di Pietro M AD - Instituto de Biologia y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina. FAU - Pascuali, Natalia AU - Pascuali N AD - Instituto de Biologia y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina. FAU - Scotti, Leopoldina AU - Scotti L AD - Instituto de Biologia y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina. FAU - Irusta, Griselda AU - Irusta G AD - Instituto de Biologia y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina. FAU - Bas, Diana AU - Bas D AD - Instituto de Biologia y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina. FAU - May, Maria AU - May M AD - Instituto de Investigaciones Farmacologicas (ININFA-UBA-CONICET), Junin 954, C1113AAD, Ciudad Autonoma de Buenos Aires, Argentina. FAU - Tesone, Marta AU - Tesone M AD - Instituto de Biologia y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina. AD - Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Guiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autonoma de Buenos Aires, Argentina. FAU - Abramovich, Dalhia AU - Abramovich D AD - Instituto de Biologia y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina. FAU - Parborell, Fernanda AU - Parborell F AD - Instituto de Biologia y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN, Ciudad Autonoma de Buenos Aires, Argentina. LA - eng PT - Journal Article PL - England TA - Mol Hum Reprod JT - Molecular human reproduction JID - 9513710 RN - 0 (Antigens, CD) RN - 0 (Cadherins) RN - 0 (Claudin-5) RN - 0 (Cldn5 protein, rat) RN - 0 (Gonadotropins, Equine) RN - 0 (Lysophospholipids) RN - 0 (N-cadherin, rat) RN - 0 (Nerve Tissue Proteins) RN - 0 (Occludin) RN - 0 (Ocln protein, rat) RN - 0 (Phosphoproteins) RN - 0 (Receptors, Lysosphingolipid) RN - 0 (S1PR1 protein, rat) RN - 0 (Sphingosine-1-Phosphate Receptors) RN - 0 (cadherin 5) RN - 0 (steroidogenic acute regulatory protein) RN - 26993-30-6 (sphingosine 1-phosphate) RN - 4G7DS2Q64Y (Progesterone) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - EC 1.1.- (3-Hydroxysteroid Dehydrogenases) RN - NGZ37HRE42 (Sphingosine) SB - IM MH - 3-Hydroxysteroid Dehydrogenases/genetics/metabolism MH - Animals MH - Antigens, CD/genetics/metabolism MH - Cadherins/genetics/metabolism MH - Capillary Permeability/*drug effects MH - Claudin-5/genetics/metabolism MH - Corpus Luteum/*drug effects/metabolism/pathology MH - Cytochrome P-450 Enzyme System/genetics/metabolism MH - Disease Models, Animal MH - Female MH - Gene Expression Regulation/drug effects MH - Gonadotropins, Equine/pharmacology MH - Humans MH - Lysophospholipids/*pharmacology MH - Nerve Tissue Proteins/genetics/metabolism MH - Occludin/genetics/metabolism MH - Organ Size MH - Ovarian Follicle/*drug effects/metabolism/pathology MH - Ovarian Hyperstimulation Syndrome/*drug therapy/genetics/metabolism/pathology MH - Phosphoproteins/genetics/metabolism MH - Pregnancy MH - Progesterone/blood MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Lysosphingolipid/genetics/metabolism MH - Sphingosine/*analogs & derivatives/pharmacology MH - Sphingosine-1-Phosphate Receptors OTO - NOTNLM OT - OHSS OT - angiogenesis OT - ovary OT - sphingolipids OT - vascular integrity EDAT- 2017/04/06 06:00 MHDA- 2018/03/14 06:00 CRDT- 2017/04/06 06:00 PHST- 2016/09/19 00:00 [received] PHST- 2017/03/29 00:00 [accepted] PHST- 2017/04/06 06:00 [pubmed] PHST- 2018/03/14 06:00 [medline] PHST- 2017/04/06 06:00 [entrez] AID - 3098063 [pii] AID - 10.1093/molehr/gax021 [doi] PST - ppublish SO - Mol Hum Reprod. 2017 Jun 1;23(6):417-427. doi: 10.1093/molehr/gax021.