ResearchBasic Science: ObstetricsA genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells
Section snippets
Peptide synthesis
Synthetic PIF analog (MVRIKPGSANKPSDD) was produced using solid-phase peptide synthesis (Peptide Synthesizer; Applied Biosystems, Foster City, CA) employing Fmoc (9-fluorenylmethoxycarbonyl) chemistry. Final purification was carried out by reversed-phase high-pressure liquid chromatography, and peptide identity was verified by mass spectrometry. Alexa Fluor 647-PIF conjugate was generated as well (Bio-Synthesis Inc, Lewisville, TX).
Endometrial cell cultures
Institutional review board approval was obtained for this
Effect of PIF on HESC
PIF 100 nmol/L significantly changed >500 genes. The genes that were significantly changed (>10-fold) are featured in Table 1. Notably, there was an 18.1-fold decrease in phosphodiesterase 4B, cyclic AMP-specific (phosphodiesterase, a gene encoding for a protein that specifically hydrolyzes cyclic AMP, a critical molecule promoting decidualization.32
We focused on 3 pathways that are relevant for implantation: (1) immune tolerance; (2) embryo adhesion; and (3) apoptosis/remodeling.
Immune pathway
PIF increased
Comment
In this study, we demonstrated that PIF affects implantation and postimplantation in decidual models. Complementary global genome and evaluable stringent proteome analysis demonstrate synergistic effects on immune, adhesion, and apoptotic/remodeling pathways in the periimplantation model (HESC) and similarly in early pregnancy (FTDC). PIF exerts more of an “adaptive” influence in FTDC by supporting protein synthesis and protecting against environmental insults.
To discern the relevance of our
Conclusion
PIF modulates, and possibly orchestrates, maternal immunity without deleterious immune suppression, prepares the local uterine environment for implantation, and creates a supportive environment for early pregnancy. Our genomic and proteomic data significantly advance understanding of PIF's essential multitargeted effects of regulating immunity, promoting embryo-decidual adhesion, and regulating adaptive apoptotic processes. Relevant putative intracellular PIF mechanistic targets were identified
Acknowledgment
The authors thank Mr Kevin Leitao for assistance in preparing the data for publication.
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Cite this article as: Paidas MJ, Krikun G, Huang SJ, et al. A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells. Am J Obstet Gynecol 2010;202:459.e1-8.
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Dr Paidas received unrestricted research funding from BioIncept LLC. This work was supported by National Institutes of Health Grant 5R01HD056123-02 (to Dr Huang).