Alterations of protein expression in serum of infants with intrauterine growth restriction and different gestational ages.
Intrauterine growth restriction (IUGR) is associated with increased morbidity and metabolic anomalies in adults. The serum proteome of venous blood was compared in 43 IUGR and 45 adequate gestational age (AGA) infants, separated into three gestational age groups, "Very Preterm" 29-32weeks, "Moderate Preterm" 33-36w, and, "Term" ≥37weeks, in samples drawn three times from birth to 1month of life. After depleting the abundant serum proteins (ProteoMiner(TM)), expression changes were studied by 2-DE, image analysis (Proteomweaver 4.0(TM)), and identification by MALDI-TOF/TOF. Significant expression differences were found in thirty-four proteins, and thirty-three were identified. Lysophospholipid acyltransferase 7 (MBOAT7), was detected exclusively in IUGR of all gestational ages and sampling times; seven other proteins were found only in AGA. Another twenty-five proteins had intensity changes ≥2.5 folds in IUGR: twenty were upregulated and five downregulated. Western blots confirmed the identification of several proteins: MBOAT7 increased 20.5-fold in IUGR, while AGA had 11.2-fold higher levels of SUMO3 and sumoylated proteins and 13.7-fold higher levels of APOL1. Upregulation of MBOAT7 in IUGR neonates could be an adaptive response to protect the brain from an adverse environment.


CONCLUSIONS
There are significant protein expression differences between IUGR and AGA at different gestational age groups and blood extraction times. The extensive upregulation of lysophospholipid acyltransferase 7 in all IUGR gestational ages and extraction times might be an adaptative response to an adverse fetal environment, reminiscent of Barker's fetal programming theory. Two serotransferrins were also upregulated in IUGR of all gestational ages. Just at birth "Very Preterm" IUGR showed nine upregulated proteins, including five albumins, apolipoprotein E, keratin type I cytoskeletal 10, solute carrier family member 2 fragment, and anaphase-promoting complex subunit 2.
Neonatology Unit, Pediatrics Service, Reina Sofía University Hospital (RSUH), Andalusian Health Service (AHS), Menéndez Pidal Avenue, 14004 Córdoba, Spain.
María D
MD
Ruis-González
Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Menéndez Pidal Avenue, 14004 Córdoba, Spain.
María D
MD
Cañete
Experimental Unit Córdoba District (EUCD), AHS, Isla Lanzarote s/n, 14011 Córdoba, Spain.
José L
JL
Gómez-Chaparro
Department of Biochemistry and Molecular Biology (DBMB-UCO), S. Ochoa Building, Rabanales Campus, University of Córdoba, A4 Highway, Km 396a, 14071 Córdoba, Spain.
Nieves
N
Abril
Pediatric Endocrinology Section, Pediatrics Service, RSUH, AHS, Menéndez Pidal Avenue, 14004 Córdoba, Spain.
Ramón
R
Cañete
Department of Biochemistry and Molecular Biology (DBMB-UCO), S. Ochoa Building, Rabanales Campus, University of Córdoba, A4 Highway, Km 396a, 14071 Córdoba, Spain. Electronic address: bb1lobaj@uco.es.
Juan
J
López-Barea
D000328:Adult; D001798:Blood Proteins / Q000096:biosynthesis*; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood*; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics
D001798:Blood Proteins; D020543:Proteome
Human newborn; Intrauterine growth restriction; Proteomics; Venous blood serum proteins