Journal article

An EG-VEGF-Dependent Decrease in Homeobox Gene NKX3.1 Contributes to Cytotrophoblast Dysfunction: A Possible Mechanism in Human Fetal Growth Restriction

Padma Murthi, Sophie Brouillet, Anita Pratt, Anthony Borg, Bill Kalionis, Frederic Goffin, Vassilis Tsatsaris, Carine Munaut, Jean-Jacques Feige, Mohamed Benharouga, Thierry Fournier, Nadia Alfaidy



Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that endocrine gland-derived vascular endothelial growth factor (EG-VEGF), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesize that EG-VEGF-dependent changes in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a homeobox gene cDNA array on placental explants of 8..

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Awarded by Australian National Health and Medical Research Council (NHMRC New Investigator project) award

Funding Acknowledgements

The authors wish to thank the consenting patients and the clinical and research midwives at the Pregnancy Research Centre, Department of Perinatal Medicine, The Royal Women's Hospital for the supply of FGR and gestation-matched control placental tissues. INSERM (U1036), University Joseph Fourier, Commissariat a L'Energie Atomique (DSV/iRTSV/BCI). Funding support was provided from Groupement des Entreprises Francaises pour la Lutte contre le Cancer Comite Isere to N Alfaidy. Funding support for this work was provided from the Australian National Health and Medical Research Council (NHMRC New Investigator project grant #509140) award to P Murthi. We also thank F Balboni and QY Zhou for their collaboration. The human placental trophoblast-derived choriocarcinoma BeWo cell line (B30 clone) was a kind gift from Stephen Rogerson, The University of Melbourne, Department of Medicine, the Royal Melbourne Hospital, Victoria, Australia. The HTR-8/SVneo cells were a kind gift from Charles Graham, Queens University, Canada.