Mol. Hum. Reprod. Advance Access originally published online on October 24, 2006
Molecular Human Reproduction 2006 12(12):763-769; doi:10.1093/molehr/gal087
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Homeobox gene DLX4 expression is increased in idiopathic human fetal growth restriction
1Pregnancy Research Centre, Department of Perinatal Medicine, The Royal Women’s Hospital, 2Department of Obstetrics and Gynaecology, The Royal Women’s Hospital and University of Melbourne, Carlton, 3Clinical Epidemiology and Biostatistics Unit, Murdoch Children’s Research Institute and University of Melbourne Department of Paediatrics, The Royal Children’s Hospital, Parkville, Victoria, Australia
4 To whom the correspondence should be addressed at: Pregnancy Research Centre, Department of Perinatal Medicine, The Royal Women’s Hospital, 132 Grattan Street, Carlton, Victoria 3053, Australia. E-mail: padma{at}unimelb.edu.au
Idiopathic fetal growth restriction (FGR) is often associated with placental insufficiency. Previously, we isolated and characterized homeobox gene DLX4 from the placenta and provided evidence that DLX4 may regulate placental development. Here, we have investigated whether DLX4 expression levels were altered in idiopathic FGR. FGR-affected placentae were collected based on strict clinical criteria. DLX4 mRNA expression was analysed in placentae obtained from pregnancies complicated by idiopathic FGR and gestation-matched control pregnancies (n = 25 each). Initial RT–PCR results showed a qualitative increase in DLX4 mRNA in both FGR-affected placentae and gestation-matched controls. Real-time PCR showed a 3-fold increase in DLX4 mRNA levels in FGR-affected placentae compared with gestation-matched controls (P < 0.005). Western immunoblotting using a rabbit DLX4 polyclonal antibody revealed significantly increased levels of DLX4 protein in term FGR-affected placentae compared with term controls [5500.1 ± 21.8 (n = 10) versus 3533.2 ± 22.4 (n = 10); P < 0.001]. Qualitative immunohistochemical analyses of term placentae showed moderately increased immunoreactivity for DLX4 antigen in the FGR-affected placentae in syncytiotrophoblasts, residual cytotrophoblast cells and endothelial cells of the fetal capillaries compared with gestation-matched control term placentae. We conclude that the increased expression of homeobox gene DLX4 may be a contributing factor to the developmental abnormalities seen in the FGR-affected placentae.
Key words: DLX4/fetal growth restriction/gene expression/homeobox/placenta