Intrauterine growth restriction modifies gene expression profiling in cord blood
Corresponding Author
Taketoshi Yoshida
Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, Toyama, Japan
Correspondence: Taketoshi Yoshida, MD PhD, Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, 2630 Sugitani, Toyama 930-0194, Japan. Email: [email protected]Search for more papers by this authorIchiro Takasaki
Division of Molecular Genetics Research, Life Science Research Center, Toyama, Japan
Search for more papers by this authorHirokazu Kanegane
Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Search for more papers by this authorSatomi Inomata
Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorYasunori Ito
Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Search for more papers by this authorKentaro Tamura
Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorMasami Makimoto
Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorShigeru Saito
Department of Gynecology and Obstetrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Search for more papers by this authorToshio Miyawaki
Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Search for more papers by this authorCorresponding Author
Taketoshi Yoshida
Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, Toyama, Japan
Correspondence: Taketoshi Yoshida, MD PhD, Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, 2630 Sugitani, Toyama 930-0194, Japan. Email: [email protected]Search for more papers by this authorIchiro Takasaki
Division of Molecular Genetics Research, Life Science Research Center, Toyama, Japan
Search for more papers by this authorHirokazu Kanegane
Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Search for more papers by this authorSatomi Inomata
Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorYasunori Ito
Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Search for more papers by this authorKentaro Tamura
Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorMasami Makimoto
Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorShigeru Saito
Department of Gynecology and Obstetrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Search for more papers by this authorToshio Miyawaki
Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Search for more papers by this authorAbstract
Background
Small-for-gestational-age (SGA) newborns are at an increased risk for perinatal morbidity and mortality and development of metabolic syndromes such as cardiovascular disease and type 2 diabetes mellitus (T2DM) in adulthood. The mechanism underlying this increased risk remains unclear. In this study, genetic modifications of cord blood were investigated to characterize fetal change in SGA newborns.
Methods
Gene expression in cord blood cells was compared between 10 SGA newborns and 10 appropriate-for-gestational-age (AGA) newborns using microarray analysis. Pathway analysis was conducted using the Ingenuity Pathways Knowledge Base. To confirm the microarray analysis results, quantitative real-time polymerase chain reaction (RT-PCR) was performed for upregulated genes in SGA newborns.
Results
In total, 775 upregulated and 936 downregulated probes were identified in SGA newborns and compared with those in AGA newborns. Of these probes, 1149 were annotated. Most of these genes have been implicated in the development of cardiovascular disease and T2DM. There was good agreement between the RT-PCR and microarray analyses results.
Conclusions
Expression of certain genes was modified in SGA newborns in the fetal period. These genes have been associated with metabolic syndrome. To clarify the association between modified gene expression in cord blood and individual vulnerability to metabolic syndrome in adulthood, these SGA newborns will be have long-term follow up for examination of genetic and postnatal environmental factors. Gene expression of cord blood can be a useful and non-invasive method of investigation of genetic alterations in the fetal period.
References
- 1
Kalkunte S, Padbury JF, Sharmav S. Immunologic basis of placental function and disease: The placenta, fetal membranes, and umbilical cord. In: CA Gleason, SU Devaskar (eds). Avery's Diseases of the Newborn, 9th edn. Elsevier Saunders, Philadelphia, 2012; 37–50.
10.1016/B978-1-4377-0134-0.10005-8 Google Scholar
- 2 Wennergren M, Wennergren G, Vilbergsson G. Obstetric characteristics and neonatal performance in a four-year small for gestational age population. Obstet. Gynecol. 1988; 72: 615–620.
- 3 Kok JH, den Ouden AL, Verloove-Vanhorick SP, Brand R. Outcome of very preterm small for gestational age infants: The first nine years of life. Br. J. Obstet. Gynaecol. 1998; 105: 162–168.
- 4 Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet 1989; 2: 577–580.
- 5 Leon DA, Lithell HO, Vâgerö D et al. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: Cohort study of 15 000 Swedish men and women born 1915–29. BMJ 1998; 317: 241–245.
- 6 Rich-Edwards JW, Stampfer MJ, Manson JE et al. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ 1997; 315: 396–400.
- 7 Stein CE, Fall CH, Kumaran K, Osmond C, Cox V, Barker DJ. Fetal growth and coronary heart disease in south India. Lancet 1996; 348: 1269–1273.
- 8 Ergaz Z, Avgil M, Ornoy A. Intrauterine growth restriction – etiology and consequences: What do we know about the human situation and experimental animal models? Reprod. Toxicol. 2005; 20: 301–322.
- 9 Langley SC, Jackson AA. Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin. Sci. (Lond.) 1994; 86: 217–222.
- 10 Nishina H, Green LR, McGarrigle HH, Noakes DE, Poston L, Hanson MA. Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep. J. Physiol. 2003; 553: 637–647.
- 11 Thompson RF, Fazzari MJ, Niu H, Barzilai N, Simmons RA, Greally JM. Experimental intrauterine growth restriction induces alterations in DNA methylation and gene expression in pancreatic islets of rats. J. Biol. Chem. 2010; 285: 15 111–152009118.
- 12 Nafee TM, Farrell WE, Carroll WD, Fryer AA, Ismail KM. Epigenetic control of fetal gene expression. BJOG 2008; 115: 158–168.
- 13 de Boo HA, Harding JE. The developmental origins of adult disease (Barker) hypothesis. Aust. N. Z. J. Obstet. Gynaecol. 2006; 46: 4–14.
- 14 Dolinoy DC, Weidman JR, Jirtle RL. Epigenetic gene regulation: Linking early developmental environment to adult disease. Reprod. Toxicol. 2007; 23: 297–307.
- 15 Tabuchi Y, Takasaki I, Kondo T. Identification of genetic networks involved in the cell injury accompanying endoplasmic reticulum stress induced by bisphenolA in testicular Sertoli cells. Biochem. Biophys. Res. Commun. 2006; 345: 1044–1050.
- 16 Han M, Liew CT, Zhang HW et al. Novel blood-based, five-gene biomarker set for the detection of colorectal cancer. Clin. Cancer Res. 2008; 14: 455–460.
- 17 Sun CJ, Zhang L, Zhang WY. Gene expression profiling of maternal blood in early onset severe preeclampsia: Identification of novel biomarkers. J. Perinat. Med. 2009; 37: 609–616.
- 18 Takasaki I, Takarada S, Fukuchi M, Yasuda M, Tsuda M, Tabuchi Y. Identification of genetic networks involved in the cell growth arrest and differentiation of a rat astrocyte cell line RCG-12. J. Cell. Biochem. 2007; 102: 1472–1485.
- 19 George EL, Georges-Labouesse EN, Patel-King RS, Rayburn H, Hynes RO. Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 1993; 119: 1079–1091.
- 20 Pankov R, Yamada KM. Fibronectin at a glance. J. Cell Sci. 2002; 115: 3861–3863.
- 21 Skilton MR, Evans N, Griffiths KA, Harmer JA, Celermajer DS. Aortic wall thickness in newborns with intrauterine growth restriction. Lancet 2005; 365: 1484–1486.
- 22 Mori A, Uchida N, Inomo A, Izumi S. Stiffness of systemic arteries in appropriate- and small-for-gestational-age newborn infants. Pediatrics 2006; 118: 1035–1041.
- 23 Visentin S, Grisan E, Zanardo V et al. Developmental programming of cardiovascular risk in intrauterine growth-restricted twin fetuses according to aortic intima thickness. J. Ultrasound Med. 2013; 32: 279–284.
- 24 Zanardo V, Visentin S, Trevisanuto D, Bertin M, Cavallin F, Cosmi E. Fetal aortic wall thickness: A marker of hypertension in IUGR children? Hypertens. Res. 2013; 36: 440–443.
- 25 Harder T, Rodekamp E, Schellong K, Dudenhausen JW, Plagemann A. Birth weight and subsequent risk of type 2 diabetes: A meta-analysis. Am. J. Epidemiol. 2007; 165: 849–857.
- 26 Cauchi S, Proença C, Choquet H et al. Analysis of novel risk loci for type 2 diabetes in a general French population: The D.E.S.I.R. study. J. Mol. Med. 2008; 86: 341–348.
- 27 Dehwah MA, Wang M, Huang QY. CDKAL1 and type 2 diabetes: A global meta-analysis. Genet. Mol. Res. 2010; 9: 1109–1120.
- 28 Prokopenko I, McCarthy MI, Lindgren CM. Type 2 diabetes: New genes, new understanding. Trends Genet. 2008; 24: 613–621.
- 29 Freathy RM, Bennett AJ, Ring SM et al. Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes 2009; 58: 1428–1433.
- 30 Andersson EA, Pilgaard K, Pisinger C et al. Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight. Diabetologia 2010; 53: 1908–1916.
- 31 Fernandez-Twinn DS, Ozanne SE. Mechanisms by which poor early growth programs type-2 diabetes, obesity and the metabolic syndrome. Physiol. Behav. 2006; 88: 234–243.
- 32 Lesage J, Blondeau B, Grino M, Bréant B, Dupouy JP. Maternal undernutrition during late gestation induces fetal overexposure to glucocorticoids and intrauterine growth retardation, and disturbs the hypothalamo-pituitary adrenal axis in the newborn rat. Endocrinology 2001; 142: 1692–1702.
- 33 Osterholm EA, Hostinar CE, Gunnar MR. Alterations in stress responses of the hypothalamic-pituitary-adrenal axis in small for gestational age infants. Psychoneuroendocrinology 2012; 37: 1719–1725.
- 34 Hayashi Y, Kajimoto K, Iida S et al. DNA microarray analysis of whole blood cells and insulin-sensitive tissues reveals the usefulness of blood RNA profiling as a source of markers for predicting type 2 diabetes. Biol. Pharm. Bull. 2010; 33: 1033–1042.
- 35 Campbell MK, Cartier S, Xie B, Kouniakis G, Huang W, Han V. Determinants of small for gestational age birth at term. Paediatr. Perinat. Epidemiol. 2012; 26: 525–533.
- 36 Gluckman PD, Hanson MA, Low FM. The role of developmental plasticity and epigenetics in human health. Birth Defects Res. C Embryo Today 2011; 93: 12–18.
- 37 Eriksson JG, Forsén T, Tuomilehto J, Osmond C, Barker DJ. Early growth and coronary heart disease in later life: Longitudinal study. BMJ 2001; 322: 949–953.
- 38 Singhal A, Cole TJ, Fewtrell M et al. Promotion of faster weight gain in infants born small for gestational age: Is there an adverse effect on later blood pressure? Circulation 2007; 115: 213–220.