Preimplantation Factor (PIF): a peptide with various functions.
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ABSTRACT:
SUBMITTER: Zare F
PROVIDER: S-EPMC7169918 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Preimplantation Factor (PIF): a peptide with various functions.
Zare Fateme F Seifati Seyed Mohammad SM Dehghan-Manshadi Mahdi M Fesahat Farzaneh F
JBRA assisted reproduction 20200501 2
Preimplantation Factor (PIF) is a novel fifteen amino acid linear peptide (MVRIKPGSANKPSDD), which has different biological functions in mammalian species e.g. its role in neuron restoration, pregnancy and related disorders, and also in autoimmune diseases. Since all clinical studies have shown that PIF has both local and systemic effects, it can be considered as an integrated therapy for the treatment of inflammation conditions, along with the prevention of advanced disease. The synthetic PIF ( ...[more]
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| S-EPMC5758471 | biostudies-literature
Project description:BackgroundViable embryos secrete preimplantation factor (PIF), a peptide that has autocrine effects where levels correlate with cultured embryos development. sPIF (PIF synthetic analog) promotes implantation by regulating decidual-cells immunity, adhesion, apoptosis and enhances trophoblastic cell invasion. Herein sPIF priming effects on non-decidualized endometrium and decidualized-stroma are investigated, assessing elements critical for effective embryo-maternal cross-talk, prior to and at implantation.MethodsWe tested sPIF effect on human non-pregnant endometrial epithelial and non-decidualized stroma α2β3 integrin expression (IHC and flow cytometry), comparing with scrambled PIF (PIFscr-control). We examined sPIF effect on decidualized non-pregnant human endometrial stromal cells (HESC) determining pro-inflammatory mediators expression and secretion (ELISA) and growth factors (GFs) expression (Affymetrix global gene array). We tested sPIF effect on HESC Phospho-kinases (BioPlex) and isolated kinases activity (FastKinase).ResultssPIF up-regulates α2β3 integrin expression in epithelial cells, (P < 0.05) while PIFscr had no effect. In contrast, in stromal cell cultures sPIF had no effect on the same. In HESC, sPIF up-regulates pro-inflammatory cytokines; IL8, IL1β and IL6 expression. The major increase in GRO-α, ICAM-1 and MCP-3 expression is coupled with same ligands secretion (P < 0.05). sPIF modulates in HESC GFs expression: up-regulates amphiregulin and epiregulin- critical for implantation and enhances several fibroblast growth factors (FGF) relevant for decidual function. In contrast, sPIF down-regulates major pro-proliferative ligands, betacellulin and IGF1 expression. sPIF modulatory effect on GFs is exerted by down-regulating pro-proliferative phospho-activated MAPkinases, p-MEK1 and p-ERK (P < 0.01, P < 0.04, respectively). Stress-induced p-38-MAPK (P = 0.04) and c-Jun kinase signaling involved MAPK8IP2 (-2.1 fold) expression decreased which protects against reactive oxygen species. Although pro-inflammatory p-NFkB (P = 0.06) decrease was mild, its promoter TNFRS11 expression markedly (-25-fold) decreased. In contrast, anti-proliferative phosphatases PTPRZ1 and PPP2R2C expression increased.ConclusionssPIF post-fertilization primes endometrial-epithelium, while during implantation creates a beneficial pro-inflammatory milieu. PIF acts by balancing decidual pro-implantation properties while controlling excessive pro-proliferative and inflammatory signals expression. Overall, PIF influences critical peri-implantation events in a sequential coordinated fashion which facilitates embryo implantation.
| S-EPMC3444419 | biostudies-literature
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