Model Placental Barrier Phenotypic Response to Fluoxetine and Sertraline: A Comparative Study
Medications taken during pregnancy may significantly impact fetal development, yet there are few studies that rigorously assess medication safety due to ethical concerns. Selective serotonin reuptake inhibitors (SSRIs) are a class of drug increasingly being prescribed for depression, yet multiple st...
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| Veröffentlicht in: | Advanced healthcare materials 2019-09, Vol.8 (18), p.e1900476-n/a |
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| creator | Arumugasaamy, Navein Gudelsky, Alana Hurley‐Novatny, Amelia Kim, Peter C. W. Fisher, John P. |
| description | Medications taken during pregnancy may significantly impact fetal development, yet there are few studies that rigorously assess medication safety due to ethical concerns. Selective serotonin reuptake inhibitors (SSRIs) are a class of drug increasingly being prescribed for depression, yet multiple studies have shown that taking SSRIs during pregnancy can lead to preterm birth and potential health concerns for the baby. Therefore, a biomimetic placental barrier model is utilized herein to assess transport profiles and phenotypic effects resulting from SSRI exposure, comparing fluoxetine and sertraline. Results show that the placental barrier quickly uptakes drug from the maternal side, but slowly releases on the fetal side. Phenotypically, there is a dose‐dependent change in cell adhesion molecule (CAM) and transforming growth factor beta (TGFβ) secretions, markers of cell adhesion and angiogenesis. Both drugs impact CAM secretions, whereas sertraline alone impacts TGFβ secretions. When evaluating cell type, it becomes clear that endothelial cells, not trophoblast, are the main cell type involved in these phenotypic changes. Overall, these findings further the understanding of SSRI transplacental transport and drug‐induced effects on the placental barrier.
This study evaluates transport of selective serotonin reuptake inhibitors (SSRIs) across the placental barrier and the effect of SSRIs on placental barrier cells. An in vitro placental barrier shows transport profiles unique to each drug, while the whole barrier and cell‐specific studies reveal drug and cell‐specific responses for both trophoblast and endothelial cells. |
| doi_str_mv | 10.1002/adhm.201900476 |
| format | Article |
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This study evaluates transport of selective serotonin reuptake inhibitors (SSRIs) across the placental barrier and the effect of SSRIs on placental barrier cells. An in vitro placental barrier shows transport profiles unique to each drug, while the whole barrier and cell‐specific studies reveal drug and cell‐specific responses for both trophoblast and endothelial cells.</description><identifier>ISSN: 2192-2640</identifier><identifier>ISSN: 2192-2659</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.201900476</identifier><identifier>PMID: 31407872</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Adhesion ; Angiogenesis ; Antidepressants ; Biomimetics ; Cell adhesion ; Cell adhesion & migration ; Cell adhesion molecules ; Cell Membrane Permeability ; Comparative studies ; Endothelial cells ; Extracellular Matrix - drug effects ; Extracellular Matrix - metabolism ; Female ; Fetuses ; Fluoxetine ; Fluoxetine - pharmacology ; Growth factors ; Human Umbilical Vein Endothelial Cells - drug effects ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Models, Biological ; Phenotype ; Placenta ; Placenta - metabolism ; Pregnancy ; Premature birth ; Secretions ; selective serotonin reuptake inhibitors ; Selective Serotonin Reuptake Inhibitors - pharmacology ; Serotonin ; Serotonin uptake inhibitors ; Sertraline ; Sertraline - pharmacology ; Tissue engineering ; Transforming Growth Factor beta - metabolism ; Transforming growth factor-b ; Transport ; Trophoblasts - drug effects ; Trophoblasts - metabolism</subject><ispartof>Advanced healthcare materials, 2019-09, Vol.8 (18), p.e1900476-n/a</ispartof><rights>2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4506-ba8cef5770ebd2675dbed481b255cc504d0c46785aade76a7200a338ebb340703</citedby><cites>FETCH-LOGICAL-c4506-ba8cef5770ebd2675dbed481b255cc504d0c46785aade76a7200a338ebb340703</cites><orcidid>0000-0001-5688-0236</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.201900476$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.201900476$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31407872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arumugasaamy, Navein</creatorcontrib><creatorcontrib>Gudelsky, Alana</creatorcontrib><creatorcontrib>Hurley‐Novatny, Amelia</creatorcontrib><creatorcontrib>Kim, Peter C. W.</creatorcontrib><creatorcontrib>Fisher, John P.</creatorcontrib><title>Model Placental Barrier Phenotypic Response to Fluoxetine and Sertraline: A Comparative Study</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Medications taken during pregnancy may significantly impact fetal development, yet there are few studies that rigorously assess medication safety due to ethical concerns. Selective serotonin reuptake inhibitors (SSRIs) are a class of drug increasingly being prescribed for depression, yet multiple studies have shown that taking SSRIs during pregnancy can lead to preterm birth and potential health concerns for the baby. Therefore, a biomimetic placental barrier model is utilized herein to assess transport profiles and phenotypic effects resulting from SSRI exposure, comparing fluoxetine and sertraline. Results show that the placental barrier quickly uptakes drug from the maternal side, but slowly releases on the fetal side. Phenotypically, there is a dose‐dependent change in cell adhesion molecule (CAM) and transforming growth factor beta (TGFβ) secretions, markers of cell adhesion and angiogenesis. Both drugs impact CAM secretions, whereas sertraline alone impacts TGFβ secretions. When evaluating cell type, it becomes clear that endothelial cells, not trophoblast, are the main cell type involved in these phenotypic changes. Overall, these findings further the understanding of SSRI transplacental transport and drug‐induced effects on the placental barrier.
This study evaluates transport of selective serotonin reuptake inhibitors (SSRIs) across the placental barrier and the effect of SSRIs on placental barrier cells. An in vitro placental barrier shows transport profiles unique to each drug, while the whole barrier and cell‐specific studies reveal drug and cell‐specific responses for both trophoblast and endothelial cells.</description><subject>Adhesion</subject><subject>Angiogenesis</subject><subject>Antidepressants</subject><subject>Biomimetics</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell adhesion molecules</subject><subject>Cell Membrane Permeability</subject><subject>Comparative studies</subject><subject>Endothelial cells</subject><subject>Extracellular Matrix - drug effects</subject><subject>Extracellular Matrix - metabolism</subject><subject>Female</subject><subject>Fetuses</subject><subject>Fluoxetine</subject><subject>Fluoxetine - pharmacology</subject><subject>Growth factors</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Models, Biological</subject><subject>Phenotype</subject><subject>Placenta</subject><subject>Placenta - metabolism</subject><subject>Pregnancy</subject><subject>Premature birth</subject><subject>Secretions</subject><subject>selective serotonin reuptake inhibitors</subject><subject>Selective Serotonin Reuptake Inhibitors - pharmacology</subject><subject>Serotonin</subject><subject>Serotonin uptake inhibitors</subject><subject>Sertraline</subject><subject>Sertraline - pharmacology</subject><subject>Tissue engineering</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Transforming growth factor-b</subject><subject>Transport</subject><subject>Trophoblasts - drug effects</subject><subject>Trophoblasts - metabolism</subject><issn>2192-2640</issn><issn>2192-2659</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LJDEQhoMoq7he9ygBL15mrKQ7Sbe3cfwERVl3j0uTTmqwJd1pk251_r2R0VnwYi6Vgqdeqh5CfjGYMgB-pO1DO-XASoBcyQ2yw1nJJ1yKcnP9z2Gb7MX4COlJwWTBfpDtjOWgCsV3yL8bb9HRO6cNdoN29ESH0GCgdw_Y-WHZN4b-xtj7LiIdPD13o3_FoemQ6s7SewxD0C61x3RG577tddBD84z0fhjt8ifZWmgXce-j7pK_52d_5peT69uLq_nsemJyAXJS68LgQigFWFsulbA12rxgNRfCGAG5BZNLVQitLSqpFQfQWVZgXWfpEMh2yeEqtw_-acQ4VG0TDTqnO_RjrDhXXGVKZkVCD76gj34MXdouUSUvMimESNR0RZngYwy4qPrQtDosKwbVu_vq3X21dp8G9j9ix7pFu8Y_TSegXAEvjcPlN3HV7PTy5n_4GzJ6j5E</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Arumugasaamy, Navein</creator><creator>Gudelsky, Alana</creator><creator>Hurley‐Novatny, Amelia</creator><creator>Kim, Peter C. 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W. ; Fisher, John P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4506-ba8cef5770ebd2675dbed481b255cc504d0c46785aade76a7200a338ebb340703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adhesion</topic><topic>Angiogenesis</topic><topic>Antidepressants</topic><topic>Biomimetics</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell adhesion molecules</topic><topic>Cell Membrane Permeability</topic><topic>Comparative studies</topic><topic>Endothelial cells</topic><topic>Extracellular Matrix - drug effects</topic><topic>Extracellular Matrix - metabolism</topic><topic>Female</topic><topic>Fetuses</topic><topic>Fluoxetine</topic><topic>Fluoxetine - pharmacology</topic><topic>Growth factors</topic><topic>Human Umbilical Vein Endothelial Cells - drug effects</topic><topic>Human Umbilical Vein Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>Models, Biological</topic><topic>Phenotype</topic><topic>Placenta</topic><topic>Placenta - metabolism</topic><topic>Pregnancy</topic><topic>Premature birth</topic><topic>Secretions</topic><topic>selective serotonin reuptake inhibitors</topic><topic>Selective Serotonin Reuptake Inhibitors - pharmacology</topic><topic>Serotonin</topic><topic>Serotonin uptake inhibitors</topic><topic>Sertraline</topic><topic>Sertraline - pharmacology</topic><topic>Tissue engineering</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Transforming growth factor-b</topic><topic>Transport</topic><topic>Trophoblasts - drug effects</topic><topic>Trophoblasts - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arumugasaamy, Navein</creatorcontrib><creatorcontrib>Gudelsky, Alana</creatorcontrib><creatorcontrib>Hurley‐Novatny, Amelia</creatorcontrib><creatorcontrib>Kim, Peter C. 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W.</au><au>Fisher, John P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Model Placental Barrier Phenotypic Response to Fluoxetine and Sertraline: A Comparative Study</atitle><jtitle>Advanced healthcare materials</jtitle><addtitle>Adv Healthc Mater</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>8</volume><issue>18</issue><spage>e1900476</spage><epage>n/a</epage><pages>e1900476-n/a</pages><issn>2192-2640</issn><issn>2192-2659</issn><eissn>2192-2659</eissn><abstract>Medications taken during pregnancy may significantly impact fetal development, yet there are few studies that rigorously assess medication safety due to ethical concerns. Selective serotonin reuptake inhibitors (SSRIs) are a class of drug increasingly being prescribed for depression, yet multiple studies have shown that taking SSRIs during pregnancy can lead to preterm birth and potential health concerns for the baby. Therefore, a biomimetic placental barrier model is utilized herein to assess transport profiles and phenotypic effects resulting from SSRI exposure, comparing fluoxetine and sertraline. Results show that the placental barrier quickly uptakes drug from the maternal side, but slowly releases on the fetal side. Phenotypically, there is a dose‐dependent change in cell adhesion molecule (CAM) and transforming growth factor beta (TGFβ) secretions, markers of cell adhesion and angiogenesis. Both drugs impact CAM secretions, whereas sertraline alone impacts TGFβ secretions. When evaluating cell type, it becomes clear that endothelial cells, not trophoblast, are the main cell type involved in these phenotypic changes. Overall, these findings further the understanding of SSRI transplacental transport and drug‐induced effects on the placental barrier.
This study evaluates transport of selective serotonin reuptake inhibitors (SSRIs) across the placental barrier and the effect of SSRIs on placental barrier cells. An in vitro placental barrier shows transport profiles unique to each drug, while the whole barrier and cell‐specific studies reveal drug and cell‐specific responses for both trophoblast and endothelial cells.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31407872</pmid><doi>10.1002/adhm.201900476</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5688-0236</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adhesion Angiogenesis Antidepressants Biomimetics Cell adhesion Cell adhesion & migration Cell adhesion molecules Cell Membrane Permeability Comparative studies Endothelial cells Extracellular Matrix - drug effects Extracellular Matrix - metabolism Female Fetuses Fluoxetine Fluoxetine - pharmacology Growth factors Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Humans Models, Biological Phenotype Placenta Placenta - metabolism Pregnancy Premature birth Secretions selective serotonin reuptake inhibitors Selective Serotonin Reuptake Inhibitors - pharmacology Serotonin Serotonin uptake inhibitors Sertraline Sertraline - pharmacology Tissue engineering Transforming Growth Factor beta - metabolism Transforming growth factor-b Transport Trophoblasts - drug effects Trophoblasts - metabolism |
| title | Model Placental Barrier Phenotypic Response to Fluoxetine and Sertraline: A Comparative Study |
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