Hostname: page-component-76fb5796d-5g6vh Total loading time: 0 Render date: 2024-04-25T12:11:27.968Z Has data issue: false hasContentIssue false

Meconium proteins as a source of biomarkers for the assessment of the intrauterine environment of the fetus

Published online by Cambridge University Press:  14 March 2018

B. Lisowska-Myjak*
Affiliation:
Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Warsaw, Poland
E. Skarżyńska
Affiliation:
Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Warsaw, Poland
M. Bakun
Affiliation:
Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
*
*Address for correspondence: Dr hab. Barbara Lisowska-Myjak, Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, ul. Banacha 1, 02-097 Warsaw, Poland. E-mail basia.myjak@interia.pl

Abstract

Intrauterine environmental factors can be associated with perinatal complications and long-term health outcomes although the underlying mechanisms remain poorly defined. Meconium formed exclusively in utero and passed naturally by a neonate may contain proteins which characterise the intrauterine environment. The aim of the study was proteomic analysis of the composition of meconium proteins and their classification by biological function. Proteomic techniques combining isoelectrofocussing fractionation and LC-MS/MS analysis were used to study the protein composition of a meconium sample obtained by pooling 50 serial meconium portions from 10 healthy full-term neonates. The proteins were classified by function based on the literature search for each protein in the PubMed database. A total of 946 proteins were identified in the meconium, including 430 proteins represented by two or more peptides. When the proteins were classified by their biological function the following were identified: immunoglobulin fragments and enzymatic, neutrophil-derived, structural and fetal intestine-specific proteins. Meconium is a rich source of proteins deposited in the fetal intestine during its development in utero. A better understanding of their specific biological functions in the intrauterine environment may help to identify these proteins which may serve as biomarkers associated with specific clinical conditions/diseases with the possible impact on the fetal development and further health consequences in infants, older children and adults.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Skogen, JC, Øverland, S. The fetal origins of adult disease: a narrative review of the epidemiological literature. JRSM Short Rep. 2012; 3, 5966.CrossRefGoogle ScholarPubMed
2. Miles, HL, Hofman, PL, Cutfield, WS. Fetal origins of adult disease: a paediatric perspective. Rev Endocr Disord. 2005; 6, 261268.Google Scholar
3. Olsen, J, David, B. (1938–2013) – a giant in reproductive epidemiology. Acta Obstet Gynecol Scand. 2014; 93, 10771080.CrossRefGoogle Scholar
4. Ng, PC, Lam, HS. Biomarkers in neonatology: the next generation of tests. Neonatology. 2012; 102, 145151.Google Scholar
5. Ostrea, EM. Understanding drug testing in the neonate and the role of meconium analysis. J Perinat Neonatal Nurs. 2001; 14, 6182.CrossRefGoogle ScholarPubMed
6. Lisowska-Myjak, B, Pachecka, J. Alpha-1-antitrypsin and IgA in serial meconium and faeces of healthy breast-fed newborns. Fetal Diagn Ther. 2007; 22, 116120.Google Scholar
7. Lisowska-Myjak, B, Pachecka, J. Trypsin and antitrypsin activities and protein concentration in serial meconium and feces of healthy newborns. J Matern Fetal Neonatal Med. 2006; 19, 477482.CrossRefGoogle ScholarPubMed
8. Laforgia, N, Baldassarre, ME, Pontrelli, G, et al. Calprotectin levels in meconium. Acta Paediatr. 2003; 92, 463466.Google Scholar
9. Lisowska-Myjak, B, Żytyńska-Daniluk, J. Changes in physiology and pathophysiology of calprotectin excretion from neonate to adult. J Mol Biomark Diagn. 2015; 6, 15.Google Scholar
10. Wessel, D, Flügge, UI. A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem. 1984; 138, 141143.Google Scholar
11. Mikula, M, Gaj, P, Dzwonek, K, et al. Comprehensive analysis of the palindromic motif TCTCGCGAGA: a regulatory element of the HNRNPK promoter. DNA Res. 2010; 17, 245260.Google Scholar
12. Brosch, M, Choudhary, J. Scoring and validation of tandem MS peptide identification methods. Methods Mol Biol. 2010; 604, 4353.CrossRefGoogle ScholarPubMed
13. Käll, L, Canterbury, JD, Weston, J, Noble, WS, MacCoss, MJ. Semi-supervised learning for peptide identification from shotgun proteomics datasets. Nat Methods. 2007; 4, 923925.Google Scholar
14. Käll, L, Storey, JD, MacCoss, MJ, Noble, WS. Assigning significance to peptides identified by tandem mass spectrometry using decoy databases. J Proteome Res. 2008; 7, 2934.Google Scholar
15. Stewart, A, Malhotra, A. Gestational diabetes and the neonate: challenges and solutions. Res Rep Neonatol. 2015; 5, 3139.Google Scholar
16. Drozdowski, LA, Clandinin, T, Thomson, ABR. Ontogeny, growth and development of the small intestine : understanding pediatric gastroenterology. World J Gastroenterol. 2010; 16, 787799.Google Scholar
17. Neu, J. Gastrointestinal development and meeting the nutritional needs of premature infants. Am J Clin Nutr. 2007; 85, 629S634S.Google Scholar
18. Lee, J, Romero, R, Lee, KA, et al. Meconium aspiration syndrome: a role for fetal systemic inflammation. Am J Obstet Gynecol. 2016; 214 , 366.e1–9.Google Scholar
19. Kääpä, P, Soukka, H. Phospholipase A2 in meconium-induced lung injury. J Perinatol. 2008; 28(Suppl. 3), S120122.Google Scholar
20. De Luca, D, Minucci, A, Tripodi, D, et al. Role of distinct phospholipases A2 and their modulators in meconium aspiration syndrome in human neonates. Intensive Care Med. 2011; 37, 11581165.Google Scholar
21. Lou, J, Mai, X, Lozoff, B, et al. Prenatal iron deficiency and auditory brainstem responses at 3 and 10 months: a pilot study. Hong Kong J Paediatr. 2016; 20, 7179.Google Scholar
Supplementary material: File

Lisowska-Myjak et al. supplementary material

Lisowska-Myjak et al. supplementary material 1

Download Lisowska-Myjak et al. supplementary material(File)
File 1.6 MB