Decorin expression is decreased in human idiopathic fetal growth restriction B. C. Swan A,D,E,F,G , P. Murthi A,B,F , G. Rajaraman A,B , N. A. Pathirage A,B , J. M. Said A,B , V. Ignjatovic C,D,E , P. T. Monagle D,E and S. P. Brennecke A,B A Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women’s Hospital, Parkville, Vic. 3052, Australia. B Department of Obstetrics and Gynaecology, The Royal Women’s Hospital, Parkville, Vic. 3052, Australia. C Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, Vic. 3052, Australia. D Department of Paediatrics, The University of Melbourne, Royal Children’s Hospital, Flemington Road, Parkville, Vic. 3052, Australia. E Department of Pathology, The University of Melbourne, Vic. 3010, Australia. F These authors contributed equally to this work. G Corresponding author. Email: padma@unimelb.edu.au Abstract. Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. Most cases of FGR are idiopathic and are associated with placental thrombosis. Previous studies suggest that proteoglycans, such as decorin, that contain the glycosaminoglycan dermatan sulfate are the principal anticoagulants in the normal placenta. The present study investigated decorin expression in placentas from pregnancies complicated by idiopathic FGR (n ¼ 26) and gestation-matched controls (n ¼ 27). Real-time polymerase chain reaction demonstrated significantly reduced decorin mRNA expression in FGR compared with control (1.52  0.14 v. 2.21  0.22, respectively; P o 0.01). Immunoblotting revealed decreased decorin protein (40 kDa) expression in FGR compared with controls (420.8  39.0 v. 690.1  42.2, respectively; n ¼ 12 in each group; P ¼ 0.0007). Immunohistochemistry demon- strated the presence of immunoreactive decorin protein in the placental villous stroma surrounding the fetal capillaries and a significant decrease in decorin protein presence in FGR compared with control (1.75  0.66 v. 2.98  1.12, respectively; n ¼ 6 in each group; P o 0.01, t-test). This is the first study to demonstrate reduced decorin in idiopathic FGR, indicating a potentially significant role for decorin in the aetiology of placental thrombosis in idiopathic FGR. Additional keywords: placenta, proteoglycan, thrombosis. Introduction Fetal growth restriction (FGR; also known as intrauterine growth restriction) is a pregnancy related disorder in which the fetus fails to achieve its full growth potential in utero. FGR is commonly defined as a birthweight of less than the 10th per- centile for gestation and is associated with an increased risk of perinatal complications, such as prematurity (Gardosi et al. 1998), stillbirth (Frøen et al. 2004), neonatal morbidity and mortality (Kramer et al. 1990; McIntire et al. 1999). Future consequences for FGR neonates include impaired neuro- psychological development. Although FGR can be attributed to fetal, placental and maternal factors, 70% of cases do not have a known cause and are designated idiopathic FGR. Idiopathic FGR has been associated with placental insufficiency (Ghidini 1996). Other features of FGR pregnancies include abnormal umbilical artery Doppler velocimetry (Salafia et al. 1997; Chen et al. 2002), oligohydramnios (Volante et al. 2004) and fetal growth asymmetry (Vik et al. 1997). Placentas from FGR pregnancies typically show fibrin deposits and thrombi in the vasculature, including uteroplacen- tal thrombosis, intervillous thrombosis, perivillous fibrin depos- its and villous stem artery thrombosis (Sugimura et al. 2001; Lanir et al. 2003). Animal and human studies have demonstrated a correlation between fibrin deposition in the placenta and reduced birthweight (Sugimura et al. 2001; Lanir et al. 2003). These haemostatic changes may compensate for increased thrombin generation and activity in idiopathic FGR pregnancies (Bellart et al. 1998). The cause of the coagulation disturbance and placental thrombosis observed in idiopathic FGR pregnan- cies is as yet unknown. In the placenta, anticoagulation mechanisms are crucial to regulate thrombin activity, minimise fibrin deposition and CSIRO PUBLISHING www.publish.csiro.au/journals/rfd Reproduction, Fertility and Development, 2010, 22, 949–955 & CSIRO 2010 10.1071/RD09240 1031-3613/10/060949