Received: December 2, 2013 Accepted after revision: February 8, 2014 Published online: March 28, 2014
Fetal Diagn Ther DOI: 10.1159/000360535
Differential Placental Gene Expression in Term Pregnancies Affected by Fetal Growth Restriction and Macrosomia Amin Sabri a, b Donna Lai b Arlene D’Silva a Sean Seeho c Jasjot Kaur a Cecilia Ng a, d Jon Hyett a, d a
Department of Obstetrics, Gynaecology and Neonatology, Queen Elizabeth II Research Institute for Mothers and Infants, b Molecular Biology Facility, Bosch Institute, c Perinatal Research Group, Kolling Institute of Medical Research, The University of Sydney, and d RPA Women and Babies, Royal Prince Alfred Hospital, Sydney, N.S.W., Australia
Abstract Introduction: Extremes of fetal growth are associated with increased perinatal mortality and morbidity and a higher prevalence of cardiovascular disease, obesity and diabetes in later life. We aimed to identify changes in placental gene expression in pregnancies with evidence of growth dysfunction and candidate genes that may be used to identify abnormal patterns of growth prior to delivery. Methods: Growth-restricted (n = 4), macrosomic (n = 6) and normal term (n = 5) placentas were selected from a banked series (n = 200) collected immediately after caesarean section. RNA was extracted prior to microarray analysis using Affymetrix HG-U219 arrays to determine variation in gene expression. Genes of interest were confirmed using qRT-PCR. Results: 338 genes in the growth-restricted and 41 genes in the macrosomic group were identified to be significantly dysregulated (>2-fold change; p < 0.05). CPXM2 and CLDN1 were upregulated and TXNDC5 and LRP2 downregulated in fetal growth restriction. In macrosomia, PHLDB2 and CLDN1 were
© 2014 S. Karger AG, Basel 1015–3837/14/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/fdt
upregulated and LEP and GCH1 were downregulated. Discussion: Dysfunctional growth is associated with differential placental gene expression and affects genes with a whole spectrum of developmental and cellular functions. Better elucidation of these pathways may allow the development of biomarkers to identify growth abnormalities and effective prenatal intervention. © 2014 S. Karger AG, Basel
Introduction
Abnormal fetal growth, resulting in fetal growth restriction (FGR) or macrosomia, is associated with an increased risk of fetal mortality and morbidity [1]. More than 50% of perinatal deaths at 2-fold change and a p value
Fetal Diagn Ther DOI: 10.1159/000360535
Differential Placental Gene Expression in Term Pregnancies Affected by Fetal Growth Restriction and Macrosomia Amin Sabri a, b Donna Lai b Arlene D’Silva a Sean Seeho c Jasjot Kaur a Cecilia Ng a, d Jon Hyett a, d a
Department of Obstetrics, Gynaecology and Neonatology, Queen Elizabeth II Research Institute for Mothers and Infants, b Molecular Biology Facility, Bosch Institute, c Perinatal Research Group, Kolling Institute of Medical Research, The University of Sydney, and d RPA Women and Babies, Royal Prince Alfred Hospital, Sydney, N.S.W., Australia
Abstract Introduction: Extremes of fetal growth are associated with increased perinatal mortality and morbidity and a higher prevalence of cardiovascular disease, obesity and diabetes in later life. We aimed to identify changes in placental gene expression in pregnancies with evidence of growth dysfunction and candidate genes that may be used to identify abnormal patterns of growth prior to delivery. Methods: Growth-restricted (n = 4), macrosomic (n = 6) and normal term (n = 5) placentas were selected from a banked series (n = 200) collected immediately after caesarean section. RNA was extracted prior to microarray analysis using Affymetrix HG-U219 arrays to determine variation in gene expression. Genes of interest were confirmed using qRT-PCR. Results: 338 genes in the growth-restricted and 41 genes in the macrosomic group were identified to be significantly dysregulated (>2-fold change; p < 0.05). CPXM2 and CLDN1 were upregulated and TXNDC5 and LRP2 downregulated in fetal growth restriction. In macrosomia, PHLDB2 and CLDN1 were
© 2014 S. Karger AG, Basel 1015–3837/14/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/fdt
upregulated and LEP and GCH1 were downregulated. Discussion: Dysfunctional growth is associated with differential placental gene expression and affects genes with a whole spectrum of developmental and cellular functions. Better elucidation of these pathways may allow the development of biomarkers to identify growth abnormalities and effective prenatal intervention. © 2014 S. Karger AG, Basel
Introduction
Abnormal fetal growth, resulting in fetal growth restriction (FGR) or macrosomia, is associated with an increased risk of fetal mortality and morbidity [1]. More than 50% of perinatal deaths at 2-fold change and a p value
