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PreImplantation Factor (PIF) promoting role in embryo implantation: increases endometrial Integrin-α2β3, amphiregulin and epiregulin while reducing betacellulin expression via MAPK in decidua

DOI: 10.1186/1477-7827-10-50

Keywords: Preimplantation Factor (PIF), Endometrium, Decidua, Gene Expression

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Abstract:

We 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).sPIF 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.sPIF 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 in

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