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Gene expression in the intestine of newborn piglets after hypoxia-reoxygenation

Pediatric Research volume 94, pages 1365–1372 (2023)Cite this article

Abstract

Background

In preterm infants, intestinal hypoxia may partly contribute to the pathophysiology of necrotizing enterocolitis through changes in gene expression. Splanchnic hypoxia can be detected with monitoring of regional splanchnic oxygen saturation (rsSO2). Using a piglet model of asphyxia, we aimed to correlate changes in rsSO2 to gene expression.

Methods

Forty-two newborn piglets were randomized to control or intervention groups. Intervention groups were subjected to hypoxia until they were acidotic and hypotensive. Next, they were reoxygenated for 30 min according to randomization, i.e., 21% O2, 100% O2, or 100% O2 for 3 min followed by 21% O2, and observed for 9 h. We continuously measured rsSO2 and calculated mean rsSO2 and variability of rsSO2 (rsCoVar = SD/mean). Samples of terminal ileum were analyzed for mRNA expression of selected genes related to inflammation, erythropoiesis, fatty acid metabolism, and apoptosis.

Results

The expression of selected genes was not significantly different between control and intervention groups. No associations between mean rsSO2 and gene expression were observed. However, lower rsCoVar was associated with the upregulation of apoptotic genes and the downregulation of inflammatory genes (P < 0.05).

Conclusion

Our study suggests that hypoxia and reoxygenation cause reduced vascular adaptability, which seems to be associated with the upregulation of apoptosis and downregulation of inflammation.

Impact

  • Our results provide important insight into the (patho)physiological significance of changes in the variability of rsSO2. Our findings may advance future research and clinical practice regarding resuscitation strategies of preterm infants.

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Fig. 1: Study protocol.
Fig. 2: Study flowchart.
Fig. 3: The course of regional splanchnic oxygen saturation throughout the study.
Fig. 4: Relative expression of inflammation-related genes in the ileum of piglets treated with 21% O2 (male: n = 3; female: n = 5), 100% O2 (30’) (male: n = 6; female: n = 4), 100% O2 (3’) (male: n = 5; female: n = 4) and control (male: n = 4; female: n = 5) between males and females.
Fig. 5: Relative expression of erythropoiesis related genes, fatty acid metabolism related genes, and apoptosis related genes in the ileum of piglets treated with 21% O2 (male: n = 3; female: n = 5), 100% O2 (30’) (male: n = 6; female: n = 4), 100% O2 (3’) (male: n = 5; female: n = 4) and control (male: n = 4; female: n = 5) between males and females.
Fig. 6: Schematic summary of the associations between lower rsCoVar during the observation period and expression of selected genes.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors wish to thank Sera Sebastian and Maria Melheim at the Oslo University Hospital Rikshospitalet, Oslo, Norway, for their contribution with the animal experiments and collection of the samples.

Funding

This study was part of the research program of the Postgraduate School for Behavioural and Cognitive Neurosciences (BCN), University of Groningen, Groningen, The Netherlands. B.M.D. was financially supported by a Junior Scientific Master Class grant of the University of Groningen. M.B. was financially supported by the China Scholarship Council.

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Author notes

  1. These authors contributed equally: Torsten Plösch, Elisabeth M. W. Kooi.

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Baukje M. Dotinga, Arend F. Bos & Elisabeth M. W. Kooi

  2. Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Mian Bao & Torsten Plösch

  3. Division of Pediatric and Adolescent Medicine, Department of Pediatric Research, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway

    Rønnaug Solberg & Ola D. Saugstad

  4. Division of Pediatric Surgery, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands

    Jan B. F. Hulscher

  5. Perinatal Neurobiology, Department of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany

    Torsten Plösch

Authors
  1. Baukje M. Dotinga
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  2. Mian Bao
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  6. Arend F. Bos
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  8. Elisabeth M. W. Kooi
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Contributions

Each author has met the Pediatric Research authorship requirements. Substantial contributions to conception and design: B.M.D., M.B., R.S., O.D.S., J.B.F.H., A.F.B., T.P., E.M.W.K. Analysis and interpretation of data: B.M.D., M.B., T.P., E.M.W.K. Drafting the article or revising it critically for important intellectual content: B.M.D., M.B., J.B.F.H., A.F.B., T.P., E.M.W.K. Final approval of the version to be published: all authors.

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Correspondence to Mian Bao.

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Dotinga, B.M., Bao, M., Solberg, R. et al. Gene expression in the intestine of newborn piglets after hypoxia-reoxygenation. Pediatr Res 94, 1365–1372 (2023). https://doi.org/10.1038/s41390-023-02657-4

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