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General Comment |
NCBI Summary:
This gene encodes a member of the G protein-coupled receptors, as well as the EDG family of proteins. The encoded protein is a receptor for sphingosine 1-phosphate, which participates in cell proliferation, survival, and transcriptional activation. Defects in this gene have been associated with congenital profound deafness. [provided by RefSeq, Mar 2016]
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Comment |
Effect of sphingosine-1-phosphate on activation of dormant follicles in murine and human ovarian tissue. Pors SE et al. (2020) In vitro activation of resting ovarian follicles, with the use of mechanical stress and/or pharmacological compounds, is an emerging and novel approach for infertility treatment. The aim of this study was to assess the sphingolipid, sphingosine-1-phosphate (S1P), as a potential in vitro activation agent in murine and human ovarian tissues and isolated follicles. Juvenile murine ovaries and donated human ovarian tissues, from 10 women undergoing ovarian tissue cryopreservation for fertility preservation, were incubated with or without 12 μM S1P for 3 hours for quantitative PCR analysis, and 12 hours for xenotransplantation or culture studies. Gene expression analyses were performed for genes downstream of the Hippo signaling pathway. Murine ovaries and isolated murine and human preantral follicles showed significantly increased mRNA expression levels of Ccn2/CCN2 following S1P treatment compared to controls. This increase was shown to be specific for the Hippo signaling pathway and for the S1P2 receptor, as co-treatment with Hippo-inhibitor, verteporfin, and S1PR2 antagonist, JTE-013, reduced the S1P-induced Ccn2 gene expression in murine ovaries. Histological evaluation of human cortical tissues (5x5x1 mm; n = 30; 3 pieces per patient) xenografted for 6 weeks and juvenile murine ovaries cultured for 4 days (n = 9) or allografted for 2 weeks (n = 48) showed no differences in the distribution of resting or growing follicles in S1P-treated ovarian tissues compared to controls. Collectively, S1P increased Ccn2/CCN2 gene expression in isolated preantral follicles and ovarian tissue from mice and human, but it did not promote follicle activation or growth in vivo. Thus, S1P does not appear to be a potent in vitro activation agent under these experimental conditions.//////////////////
Follicular fluid high-density lipoprotein-associated sphingosine 1-phosphate (S1P) promotes human granulosa lutein cell migration via S1P receptor type 3 and small G-protein RAC1. Becker S 2011 et al.
Coordinated migration and progesterone production by granulosa cells is critical to the development of the corpus luteum, but the underlying mechanisms remain obscure. Sphingosine 1-phosphate (S1P), which is associated with follicular fluid high-density lipoprotein (FF-HDL), was previously shown to regulate ovarian angiogenesis. We herein examined the effects of S1P and FF-HDL on the function of granulosa lutein cells. Both FF-HDL and S1P induced migration of primary human granulosa lutein cells (hGCs) and the granulosa lutein cell line HGL5. In addition, FF-HDL but not S1P promoted progesterone synthesis, and neither of the two compounds stimulated proliferation of granulosa lutein cells. Polymerase chain reaction and Western blot experiments demonstrated the expression of S1P receptor type 1 (S1PR1), S1PR2, S1PR3, and S1PR5 but not S1PR4 in hGCs and HGL5 cells. The FF-HDL- and S1P-induced granulosa lutein cell migration was emulated by FTY720, an agonist of S1PR1, S1PR3, S1PR4, and S1PR5, and by VPC24191, an agonist of S1PR1 and S1PR3, but not by SEW2871 and phytosphingosine 1-phosphate, agonists of S1PR1 and S1PR4, respectively. In addition, blockade of S1PR3 with CAY1044, suramine, or pertussis toxin inhibited hGC and HGL5 cell migration toward FF-HDL or S1P, while blockade of S1PR1 and S1PR2 with W146 and JTE013, respectively, had no effect. Both FF-HDL and S1P triggered activation of small G-protein RAC1 and actin polymerization in granulosa cells, and RAC1 inhibition with Clostridium difficile toxin B or NSC23766 abolished FF-HDL- and S1P-induced migration. The FF-HDL-associated S1P promotes granulosa lutein cell migration via S1PR3 and RAC1 activation. This may represent a novel mechanism contributing to the development of the corpus luteum.
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