A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells.
OBJECTIVE
Preimplantation factor (PIF) is a novel, 15 amino acid peptide, secreted by viable embryos. This study aims to elucidate PIF's effects in human endometrial stromal cells (HESC) decidualized by estrogen and progestin, which mimics the preimplantation milieu, and in first-trimester decidua cultures (FTDC).


METHODS
HESC or FTDC were incubated with 100 nmol/L synthetic PIF or vehicle control. Global gene expression was analyzed using microarray and pathway analysis. Proteins were analyzed using quantitative mass spectrometry, and PIF binding by protein array.


RESULTS
Gene and proteomic analysis demonstrate that PIF affects immune, adhesion, and apoptotic pathways. Significant up-regulation in HESC (fold change) include: nuclear factor-k-beta activation via interleukin-1 receptor-associated kinase binding protein 1 (53); Toll-like receptor 5 (9); FK506 binding protein 15, 133kDa protein (2.3); and Down syndrome cell adhesion molecule like 1 (16). B-cell lymphoma protein 2 was down-regulated in HESC (21.1) and FTDC (27.1). Protein array demonstrates PIF interaction with intracellular targets insulin-degrading enzyme and beta-K+ channels.


CONCLUSIONS
PIF displays essential multitargeted effects, of regulating immunity, promoting embryo-decidual adhesion, and regulating adaptive apoptotic processes.
Paidas
Michael J
MJ
Yale Women and Children's Center for Blood Disorders, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA. michael.paidas@yale.edu
Krikun
Graciela
G
Huang
S Joseph
SJ
Jones
Richard
R
Romano
Michael
M
Annunziato
Jack
J
Barnea
Eytan R
ER
D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology*; D015536:Down-Regulation / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D010455:Peptides / Q000502:physiology*; D011247:Pregnancy / Q000502:physiology*; D040081:Protein Array Analysis; D040901:Proteomics; D017154:Stromal Cells / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D010455:Peptides; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2
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