Sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization
Sphingosine and sphingosine-1-phosphate (S1P) are involved in regulating cell differentiation. This study postulated that changes in sphingolipid biosynthesis and metabolism are important in trophoblast syncytialization and therefore examined the production, metabolism and actions of sphingosine and...
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| Format: | Journal Article |
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Elsevier
2012
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| Online Access: | http://www.elsevier.com/locate/rbmo/ http://hdl.handle.net/20.500.11937/10890 |
| _version_ | 1848747657975037952 |
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| author | Singh, A. Dharmarajan, Arunasalam Aye, I. Keelan, J. |
| author_facet | Singh, A. Dharmarajan, Arunasalam Aye, I. Keelan, J. |
| author_sort | Singh, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Sphingosine and sphingosine-1-phosphate (S1P) are involved in regulating cell differentiation. This study postulated that changes in sphingolipid biosynthesis and metabolism are important in trophoblast syncytialization and therefore examined the production, metabolism and actions of sphingosine and S1P during spontaneous trophoblast differentiation and fusion in vitro. Significantdeclines in intracellular sphingosine concentration (P 0.05) and sphingosine kinase 1 (SPHK1) expression (P 0.01) were observed during trophoblast syncytialization. Secreted S1P concentrations dropped steeply after 72 h, before rising to basal concentrations with syncytialization. Intracellular S1P concentrations were undetectable throughout. Treating cells with exogenous sphingosine (P 0.01), S1P (P 0.001) or a specific SPHK1 inhibitor (P 0.05) for up to 72 h in culture significantly inhibited trophoblast differentiation (measured as reduced human chorionic gonadotrophin production); effects on other biochemical and morphological markers of differentiation were absent or inconsistent. Phosphorylation of Akt, an established down-stream target of S1P that spontaneously declines with trophoblast differentiation, was markedly reduced by S1P (P 0.05). In conclusion, changes in the sphingosine–S1P pathway are involved in the regulation of trophoblast differentiation in term human placenta. Dysregulation of sphingolipid homeostasis could, therefore, disrupt placental formation and function with deleterious consequences for pregnancyoutcome. |
| first_indexed | 2025-11-14T06:52:38Z |
| format | Journal Article |
| id | curtin-20.500.11937-10890 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:52:38Z |
| publishDate | 2012 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-108902017-02-28T01:33:14Z Sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization Singh, A. Dharmarajan, Arunasalam Aye, I. Keelan, J. sphingosine kinase placenta sphingosine-1-phosphate trophoblast differentiation sphingosine Sphingosine and sphingosine-1-phosphate (S1P) are involved in regulating cell differentiation. This study postulated that changes in sphingolipid biosynthesis and metabolism are important in trophoblast syncytialization and therefore examined the production, metabolism and actions of sphingosine and S1P during spontaneous trophoblast differentiation and fusion in vitro. Significantdeclines in intracellular sphingosine concentration (P 0.05) and sphingosine kinase 1 (SPHK1) expression (P 0.01) were observed during trophoblast syncytialization. Secreted S1P concentrations dropped steeply after 72 h, before rising to basal concentrations with syncytialization. Intracellular S1P concentrations were undetectable throughout. Treating cells with exogenous sphingosine (P 0.01), S1P (P 0.001) or a specific SPHK1 inhibitor (P 0.05) for up to 72 h in culture significantly inhibited trophoblast differentiation (measured as reduced human chorionic gonadotrophin production); effects on other biochemical and morphological markers of differentiation were absent or inconsistent. Phosphorylation of Akt, an established down-stream target of S1P that spontaneously declines with trophoblast differentiation, was markedly reduced by S1P (P 0.05). In conclusion, changes in the sphingosine–S1P pathway are involved in the regulation of trophoblast differentiation in term human placenta. Dysregulation of sphingolipid homeostasis could, therefore, disrupt placental formation and function with deleterious consequences for pregnancyoutcome. 2012 Journal Article http://hdl.handle.net/20.500.11937/10890 http://www.elsevier.com/locate/rbmo/ Elsevier restricted |
| spellingShingle | sphingosine kinase placenta sphingosine-1-phosphate trophoblast differentiation sphingosine Singh, A. Dharmarajan, Arunasalam Aye, I. Keelan, J. Sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization |
| title | Sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization |
| title_full | Sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization |
| title_fullStr | Sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization |
| title_full_unstemmed | Sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization |
| title_short | Sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization |
| title_sort | sphingosine–sphingosine-1-phosphate pathway regulates trophoblast differentiation and syncytialization |
| topic | sphingosine kinase placenta sphingosine-1-phosphate trophoblast differentiation sphingosine |
| url | http://www.elsevier.com/locate/rbmo/ http://hdl.handle.net/20.500.11937/10890 |