Homeobox gene transforming growth factor β-induced factor-1 (TGIF-1) is a regulator of villous trophoblast differentiation and its expression is increased in human idiopathic fetal growth restriction | Zendy

Niroshani Pathirage | Zendy; M. Cocquebert | Zendy; Yoel Sadovsky | Zendy; Mohamed Abumaree | Zendy; Ursula Manuelpillai | Zendy; Anthony J. Borg | Zendy; Rosemary J. Keogh | Zendy; Shaun P. Brennecke | Zendy; Danièle EvainBrion | Zendy; Thierry Fournier | Zendy; Bill Kalionis | Zendy; Padma Murthi | Zendy

Open Access

Homeobox gene transforming growth factor β-induced factor-1 (TGIF-1) is a regulator of villous trophoblast differentiation and its expression is increased in human idiopathic fetal growth restriction

Author(s) -

Niroshani Pathirage,

M. Cocquebert,

Yoel Sadovsky,

Mohamed Abumaree,

Ursula Manuelpillai,

Anthony J. Borg,

Rosemary J. Keogh,

Shaun P. Brennecke,

Danièle EvainBrion,

Thierry Fournier,

Bill Kalionis,

Padma Murthi

Publication year - 2013

Publication title -

molecular human reproduction

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.143

H-Index - 122

eISSN - 1460-2407

pISSN - 1360-9947

DOI - 10.1093/molehr/gat042

Subject(s) - biology , trophoblast , syncytiotrophoblast , endocrinology , medicine , homeobox , placenta , cytotrophoblast , andrology , gene expression , microbiology and biotechnology , fetus , gene , genetics , pregnancy

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.

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