Am J Perinatol 2016; 33 - A023
DOI: 10.1055/s-0036-1592394

Transcriptomics and Metabolomics of Congenital Diaphragmatic Hernia

F. Piersigilli 1, *, M. Syed 1, *, V. Mondi 2, I. Capolupo 2, F. Campi 2, O. Danhaive 2, P. Bagolan 2, A. Dotta 2, C. Auriti 2, L. TuKiet 3, V. Bhandari 1, *
  • 1Department of Pediatrics and Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT, US
  • 2Department of neonatology, Bambino Gesu’ Children’s Hospital, Rome, Italy
  • 3MS and Proteomics Resource, Yale University, New Haven, CT, US
  • *Current affiliation: Drexel University College of Medicine, Philadelphia, Pennsylvania

Presenter: Fiammetta Piersigilli (e-mail: fiammetta.piersigilli@opbg.net)

Introduction: Transcriptomics and metabolomics are promising “omic” approaches that can help elucidate the signaling pathways involved in the pathogenesis of congenital diaphragmatic hernia (CDH). The transcriptome is the complete set of RNA transcripts. In particular, miRNAs are small non-coding RNAs (21–25 nt) that inhibit protein expression at the post-transcriptional level. Metabolomics consists of the quantitative analysis of a large number of low molecular mass metabolites to identify changes in the composition of metabolites caused by the interaction between specific pathophysiological states, gene expression, and environment.

Materials and Methods: The aim of the study was to use an “omic” approach to identify some new signaling pathways involved in CDH. We performed a prospective pilot study on tracheal aspirate samples collected in the first 2 days of life in patients with CDH, compared with age-matched control patients. The cell pellet was used to study the cluster miR17–92 (consisting of miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a-1), as this cluster of miRs have been linked to pulmonary hypertension, a complication often associated with CDH. We performed a non-targeted metabolomics profile on the supernatant of the tracheal aspirate samples.

Results: Ten patients with CDH and 12 controls (neonates with perinatal asphyxia or with esophageal atresia) were recruited. Cluster miR17–92 had an altered expression in CDH patients: miR 16a, miR 17, miR-18a, miR-19b-1, and miR-20a had an approximately 2-fold decreased expression (p < 0.05) in CDH patients, compared with controls. miR had a decreased expression in CXDH patients compared with controls, but difference was not significant (p > 0.05). On the contrary, miR 19a had a greater expression (p < 0.05) in CDH patients compared with controls. From a metabolomics point of view, we found a statistical significant difference in the composition of acylcarnitines in five CDH-affected patients versus five controls.

Conclusion: Specific patterns of miRNA expression and metabolites profile can be discerned in tracheal aspirate samples in infants with CDH, compared with controls. Given the small sample size, our data needs to be confirmed with a larger sample size.

Keywords: miR, CDH, transcriptomics