engleski

Expression of DVL1, DVL2 and DVL3 proteins in placentas with intrauterine growth restriction

Dishevelled proteins (DVL) are positive regulators and central mediators in Wnt signaling pathway that has an important role in placental development and trophoblast differentiation. Since Wnt pathway promotes cell invasion, its reduced activation has been associated with unsuccessful trophoblast invasion, a phenomena observed in placentas of fetuses with intrauterine growth restriction (IUGR). To further understand the molecular background of invasive processes, herein we have examined the gene expression of DVL1, DVL2 and DVL3 homologues in archival, formalin-fix and paraffin-embedded tissue samples of 15 term placentas with IUGR and equal number of normal pathologically unaltered term placentas. The DVL1, DVL2 and DVL3 mRNA expression levels were analyzed by qPCR, and the protein expressions levels were semi-quantitatively analyzed by immunohistochemical approach. Protein expression of DVL2 and DVL3 was significantly higher in trophoblasts in placental villi from IUGR pregnancies compared with the control group of term Dishevelled proteins (DVL) are positive regulators and central mediators in Wnt signaling pathway that has an important role in placental development and trophoblast differentiation. Since Wnt pathway promotes cell invasion, its reduced activation has been associated with unsuccessful trophoblast invasion, a phenomena observed in placentas of fetuses with intrauterine growth restriction (IUGR). To further understand the molecular background of invasive processes, herein we have examined the gene expression of DVL1, DVL2 and DVL3 homologues in archival, formalin-fix and paraffin-embedded tissue samples of 15 term placentas with IUGR and equal number of normal pathologically unaltered term placentas. The DVL1, DVL2 and DVL3 mRNA expression levels were analyzed by qPCR, and the protein expressions levels were semi-quantitatively analyzed by immunohistochemical approach. Protein expression of DVL2 and DVL3 was significantly higher in trophoblasts in placental villi from IUGR pregnancies compared with the control group of term placentas, while DVL3 protein expression was significantly higher in endothelial cells in placental villi from IUGR pregnancies compared with normal placentas. Regarding the DVL3 protein expression, intense immunohistochemical staining was detected in stem villous stroma of IUGR placentas. Its weaker staining was observed in terminal villous stroma of IUGR tissue samples, while the very weak DVL3 staining pattern was observed in stem and terminal villous stroma of normal placentas. There was no statistically significant difference in mRNA expression of either DVL1, DVL2 or DVL3 between normal and IUGR placentas. Our data indicate that DVL proteins are actively involved in pathogenesis of IUGR pregnancies.

placenta ; IUGR ; Wnt signaling pathway ; DVL1 ; DVL2 ; DVL3

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