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(American Journal of Pathology. 2006;168:511-518.)
© 2006 American Society for Investigative Pathology

Homeobox Gene HLX1Expression Is Decreased in Idiopathic Human Fetal Growth Restriction

Padma Murthi*{dagger}, Vicki Doherty*, Joanne Said*{dagger}, Susan Donath{ddagger}, Shaun P. Brennecke*{dagger} and Bill Kalionis*{dagger}

From the Department of Perinatal Medicine,* Pregnancy Research Centre, The Royal Women’s Hospital, Carlton, Victoria; the Department of Obstetrics and Gynaecology,{dagger} University of Melbourne, The Royal Women’s Hospital Campus, Carlton, Victoria; and the Clinical Epidemiology and Biostatistics Unit,{ddagger} Royal Children’s Hospital, Parkville, Victoria, Australia

Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. Identifiable causes of FGR account for ~30% of cases, but the remainder are idiopathic and are frequently associated with placental malfunction. Previously, we isolated the homeobox gene HLX1 and provided evidence for a regulatory role in normal placental development. Here, we investigated whether placental HLX1 expression levels are changed in placentas from idiopathic FGR pregnancies. Real-time polymerase chain reaction quantitation showed reduced HLX1 mRNA levels with advancing gestation age (preterm control placentas, 27 to 35 weeks, 1.1 ± 0.3, n = 13, versus term placentas 36 to 41 weeks, 0.74 ± 0.02, n = 12, P < 0.005). FGR-affected placentas had significantly lower levels of HLX1 expression compared with gestation age-matched controls (0.36 ± 0.07 versus 1.05 ± 0.2, n = 25, P < 0.001). Immunoblotting with a rabbit polyclonal HLX1 antibody revealed reduced levels of HLX1 in FGR-affected placentas compared with controls (481.07 ± 12.3 versus 2766.7 ± 30.3, n = 10, P < 0.001). Immunohistochemistry showed a qualitative decrease in HLX1 immunoreactivity in FGR-affected term placentas compared with controls. This is the first demonstration that a homeobox transcriptional regulator shows altered expression in an important human placental disorder, suggesting that decreased HLX1 levels contribute to the abnormalities in placental developmental seen in idiopathic FGR.





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