sphingosine-1-phosphate and Ovarian-Diseases

Sphingosine-1-phoshate (S1P) is a membrane sphingolipid involved in several physiological processes, including cell proliferation, tissue growth, cell survival and migration, inflammation, vasculogenesis, and angiogenesis. Herein, we review the most critical effects of S1P on ovarian function, including its physiological and pathophysiological effects. Based on the available evidence, S1P plays an important role in ovarian physiology, participating as an essential stimulator of follicular development in both the preantral and antral phases, as well as in ovulation and corpus luteum development. Moreover, S1P may be a good cytoprotective agent against cancer treatment side-effects (chemotherapy with or without radiation therapy). In the future, this compound may be given for fertility preservation to women undergoing cancer treatment. However, further studies are required to confirm its efficacy in ovarian protection and also its safety in terms of cancer prognosis, given the biological action of the compound. Under- or over-production of S1P may be related to ovarian pathologies.

Topics: Animals; Cell Proliferation; Corpus Luteum; Female; Fertility Preservation; Humans; Lysophospholipids; Ovarian Diseases; Ovarian Follicle; Ovarian Neoplasms; Ovary; Sphingosine; Sphingosine-1-Phosphate Receptors

Oocytes are highly radiosensitive, so agents that prevent radiation-induced ovarian follicle destruction are important fertility preservation strategies. A previous study in rhesus macaques demonstrated that ovarian treatment with antiapoptotic agents, sphingosine-1-phosphate (S1P) and FTY720, its long-acting mimetic, preserved follicles following a single dose of 15 Gy X-ray radiation, and live offspring were obtained from FTY720-treated animals. However, it is unknown whether these antiapoptotic agents also protected the ovarian stroma from late effects of radiation, including vascular damage and fibrosis. Using ovarian histological sections from this study, we evaluated the vasculature and extracellular matrix in the following cohorts: vehicle + sham irradiation, vehicle + irradiation (OXI), S1P + irradiation (S1P), and FTY720 + irradiation (FTY720). One ovary from each animal was harvested prior to radiation whereas the contralateral ovary was harvested 10 months post-treatment. We assessed vasculature by immunohistochemistry with a PECAM1 antibody, hyaluronan by a hyaluronan binding protein assay, and collagen by picrosirius red and Masson's trichrome staining. Disorganized vessels were observed in the medulla in the OXI and S1P cohorts relative to the sham, but the vasculature in the FTY720 cohort appeared intact, which may partially explain fertoprotection. There were no differences in the hyaluronan matrix among the cohorts, but there was thickening of the tunica albuginea and fibrosis in the OXI cohort relative to the sham, which was not mitigated by either S1P or FTY720 treatment. Thus, the fertoprotective properties of S1P and FTY720 may be limited given their inability to protect the ovarian stroma against the late effects of radiation-induced fibrosis.

Topics: Animals; Female; Fibrosis; Fingolimod Hydrochloride; Immunosuppressive Agents; Lysophospholipids; Macaca mulatta; Ovarian Diseases; Sphingosine; Sphingosine 1 Phosphate Receptor Modulators

To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.. A case-control laboratory study.. Tertiary care university hospital.. A total of 31 women, with (n = 16) and without (n = 15) endometriosis took part in the study.. After surgical excision with pathological analysis, endometrial specimens were obtained from women affected or not by endometriosis.. SPHK1-2, SGPP1-2, SGPL1, SPHKAP, and S1PR1-5 messenger RNA expression by quantitative real-time polymerase chain reaction (PCR) in the endometrium of 15 disease-free women, 16 eutopic and 16 ectopic endometrium of endometriosis-affected women. The S1PR1 and S1PR2 expression were further investigated by immunohistochemistry.. The SGPP2 expression was decreased in eutopic and ectopic endometrium of endometriosis-affected women (1.7- and 16.7-fold, respectively). The SGPP1, weakly expressed in healthy endometrium, is up-regulated in endometriosis-affected women (11.9- and 64.7-fold, respectively), but its expression remains low. The SGPL1 expression was decreased in ectopic endometrium (3.3-fold) and SPHKAP expression was increased in ectopic endometrium (112.6-fold) compared with endometrium of disease-free women. In endometriosis-affected women, S1PR3 expression was decreased in eutopic and ectopic endometrium (2.1- and 6.3-fold, respectively); S1PR2 and S1PR1 expression was increased in eutopic (2.5-fold) and ectopic endometrium (2.6-fold). These increases were confirmed at the protein levels by immunohistochemistry.. Expression of the enzymes implicated in the regulation of the sphingosine-1-phosphate level balance and of its receptors is overall heavily deregulated in endometriotic lesions in favor of a decreased sphingosine-1-phosphate catabolism. Our results plead for a role of the sphingosine pathway in establishing and survival of endometriotic lesions.

Topics: Aldehyde-Lyases; Analysis of Variance; Case-Control Studies; Endometriosis; Endometrium; Female; Hospitals, University; Humans; Immunohistochemistry; Lysophospholipids; Membrane Proteins; Ovarian Diseases; Paris; Phosphoric Monoester Hydrolases; Phosphotransferases (Alcohol Group Acceptor); Real-Time Polymerase Chain Reaction; Receptors, Lysosphingolipid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sphingosine; Sphingosine-1-Phosphate Receptors

The aim of this study was to assess the possible protective effect of sphingosine-1-phosphate (S1P), a polar sphingoid metabolite that seemingly promotes cell survival, on cytotoxin- and irradiation-induced ovarian injury in the rat model. Administration of S1P into ovarian bursa before whole-body irradiation led to decreased percentage of apoptotic cells, mostly in primordial follicles; however, S1P was not effective against apoptosis in rats that were given intraperitoneal cyclophosphamide.

Topics: Animals; Antineoplastic Agents, Alkylating; Apoptosis; Cyclophosphamide; Disease Models, Animal; Female; Injections, Intraperitoneal; Lysophospholipids; Ovarian Diseases; Ovarian Follicle; Ovulation Induction; Radiation Injuries, Experimental; Rats; Rats, Wistar; Sphingosine; Whole-Body Irradiation