A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells

Abstract

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).

Study design: 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.

Conclusion: PIF displays essential multitargeted effects, of regulating immunity, promoting embryo-decidual adhesion, and regulating adaptive apoptotic processes.

Figure 1. PIF-induced modulation of the TLR5 pathway in HESC

Green reflects downregulation while red reflects upregulation. The intensity of the color reflects the extent of change in mRNA detection. Ingenuity Systems Inc. Redwood Ca.

Figure 2. PIF-induced modulation of the BCL2 pathway in HESC

Green reflects downregulation while red reflects upregulation. The intensity of the color reflects the extent of change in mRNA detection. Ingenuity Systems Inc. Redwood Ca.

Figure 3. PIF-induced increase in TLR-2 expression in FTDC

Increases in both 10 and 100nM PIF doses were noted as examined by Western blot. This reflects PIF antipathogenic effect on the early pregnancy milieu.

Figure 4. PIF-induced modulation of the BCL2 pathway in FTDC

Green reflects downregulation while red reflects upregulation. The intensity of the color reflects the extent of change in mRNA detection. Ingenuity Systems Inc. Redwood Ca.