Obstetrics and Gynaecology - Research Publications

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    Homeobox gene transforming growth factor -induced factor-1 (TGIF-1) is a regulator of villous trophoblast differentiation and its expression is increased in human idiopathic fetal growth restriction
    Pathirage, NA ; Cocquebert, M ; Sadovsky, Y ; Abumaree, M ; Manuelpillai, U ; Borg, A ; Keogh, RJ ; Brennecke, SP ; Evain-Brion, D ; Fournier, T ; Kalionis, B ; Murthi, P (OXFORD UNIV PRESS, 2013-10)
    Abnormal trophoblast function is associated with human fetal growth restriction (FGR). Targeted disruption of homeobox gene transforming growth β-induced factor (TGIF-1) results in placental dysfunction in the mouse. The role of human TGIF-1 in placental cell function is unknown. The aims of this study were to determine the expression of TGIF-1 in human idiopathic FGR-affected placentae compared with gestation-matched controls (GMC), to elucidate the functional role of TGIF-1 in trophoblasts and to identify its downstream targets. Real-time PCR and immunoblotting revealed that TGIF-1 mRNA and protein expression was significantly increased in FGR-affected placentae compared with GMC (n = 25 in each group P < 0.05). Immunoreactive TGIF-1 was localized to the villous cytotrophoblasts, syncytiotrophoblast, microvascular endothelial cells and in scattered stromal cells in both FGR and GMC. TGIF-1 inactivation in BeWo cells using two independent siRNA resulted in significantly decreased mRNA and protein of trophoblast differentiation markers, human chorionic gonadotrophin (CGB/hCG), syncytin and 3β-hydroxysteroid dehydrogenase/3β-honest significant difference expression. Our data demonstrate that homeobox gene TGIF-1 is a potential up-stream regulator of trophoblast differentiation and the altered TGIF-1 expression may contribute to aberrant villous trophoblast differentiation in FGR.