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dc.contributor.authorMenkhorst, EM
dc.contributor.authorLane, N
dc.contributor.authorWinship, AL
dc.contributor.authorLi, P
dc.contributor.authorYap, J
dc.contributor.authorMeehan, K
dc.contributor.authorRainczuk, A
dc.contributor.authorStephens, A
dc.contributor.authorDimitriadis, E
dc.date.accessioned2020-12-10T01:52:53Z
dc.date.available2020-12-10T01:52:53Z
dc.date.issued2012-02-16
dc.identifierpii: PONE-D-11-23334
dc.identifier.citationMenkhorst, E. M., Lane, N., Winship, A. L., Li, P., Yap, J., Meehan, K., Rainczuk, A., Stephens, A. & Dimitriadis, E. (2012). Decidual-Secreted Factors Alter Invasive Trophoblast Membrane and Secreted Proteins Implying a Role for Decidual Cell Regulation of Placentation. PLOS ONE, 7 (2), https://doi.org/10.1371/journal.pone.0031418.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/253826
dc.description.abstractInadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the 'extravillous trophoblast' (EVT) invade through the differentiated uterine endometrium (the decidua) to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10(-8) M), medroxyprogesterone acetate (10(-7) M) and cAMP (0.5 mM) for 14 days. Conditioned media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM) of treatment. Isolated primary EVT cultured on Matrigel™ were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1 (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro-inflammatory condition. Overall, we have demonstrated the potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.titleDecidual-Secreted Factors Alter Invasive Trophoblast Membrane and Secreted Proteins Implying a Role for Decidual Cell Regulation of Placentation
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0031418
melbourne.affiliation.departmentObstetrics and Gynaecology
melbourne.source.titlePLoS One
melbourne.source.volume7
melbourne.source.issue2
dc.rights.licenseCC BY
melbourne.elementsid1358186
melbourne.contributor.authorDimitriadis, Evdokia
melbourne.contributor.authorMenkhorst, Ellen
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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