Local Sphingosine 1-phosphate (S1P) administration affects follicular/luteal development and enhances vascular integrity in ovarian hyperstimulation syndrome (OHSS)

DI PIETRO M, SCOTTI L, PASCUALI N, BAS D, IRUSTA G, TESONE M, ABRAMOVICH D AND PARBORELL F

Chascomus

Jornada; XVI Jornada Anual de la Sociedad Argentina de Biología (SAB); 2014

Sociedad Argentina de Biología (SAB).

OHSS remains the most serious complication of gonadotropin treatment. Despite advances in prediction and management of OHSS, complete prevention has not been possible yet. The main clinical components are marked enlargement of the ovaries, with luteal and hemorrhagic cysts, and an excessive fluid shift. This shift is caused by increased vascular permeability in response to hormonal stimulation. S1P is an active lysophospholipid that exerts pleiotropic effects including cell proliferation, cell survival, cell migration and cell adhesion. Previously, we observed decreased S1P levels in ovarian follicular fluid (FF) from OHSS patients. The aim of this study was to investigate the effects of S1P administration on the follicular and luteal development, cystic structures, peri-endothelial cell area, S1P1/3 receptors, sphingosine lyase (Sly)and kinase (Sk), n-cadherin, nectin-2 and occludin levels in ovaries from an OHSS rat model. Sprague Dawley rats were injected prepubertal eCG (10 IU) and 48 hours later with hCG (10 IU) (Control). The OHSS group was injected with eCG (50 IU / day) for 4 consecutive days and 24 hours later with hCG (25 IU). The group OHSS + S1P received S1P (5ul/ovary; 1mM) under the bursa of one ovary in the day of hCG inyection. The rats were sacrificed 24 h. post hCG. Ovaries were isolated for histological sections to detect α-actin (cell periendothelial marker) by IHQ and to isolate proteins by western blot. S1P decreased significantly the percentage of corpora lutea and cyst structures  compared to OHSS group alone (p<?and p<?., respectively). No significant changes were observed in the percentage of preantral and early antral follicles. S1P treatment did not affect peri-endothelial area. S1P injection increased N-cadherin and occludin levels whereas nectin-2 levels did not change compared to OHSS group without treatment. In OHSS group, the levels of Sly and Sk were unaffected by S1P. In addition, S1P increased levels of its own receptor, S1P1, regarding OHSS group alone. In conclusion, our findings indicate that ovarian S1P administration prevents the early onset of OHSS and decreases its severity in rats.