decidual-secreted factors alter invasive trophoblast membrane and secreted proteins implying a role for decidual cell regulation of placentationdecidual-secreted因素改变入侵滋养层膜和分泌蛋白暗示蜕膜细胞调节胎座式的角色.pdf

Decidual-Secreted Factors Alter Invasive Trophoblast Membrane and Secreted Proteins Implying a Role for Decidual Cell Regulation of Placentation Ellen Melaleuca Menkhorst, Natalie Lane, Amy Louise Winship, Priscilla Li, Joanne Yap, Katie Meehan, Adam Rainczuk, Andrew Stephens, Evdokia Dimitriadis* Prince Henry’s Institute, Clayton, Victoria, Australia Abstract Inadequate 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 (1028 M), medroxyprogesterone acetate (1027 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 MatrigelTM 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),