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Gut inflammation and expression of ICC in a fetal lamb model of fetoscopic intervention for gastroschisis

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Abstract

Background

The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel formation and disorganization of interstitial Cajal cells (ICC) have been proposed in humans. The aim of this study was to evaluate the impact of prenatal coverage of gastroschisis on gut inflammation and expression of ICC in a fetal lamb model.

Methods

Twenty-one German blackhead sheep with an abdominal wall defect that was created fetoscopically on day 77 of 145 days gestation were used in this study. Intrauterine surgery with the aim to cover the defect was performed 3 weeks later; two fetuses were covered completely, 5 partially and 11 remained uncovered. Three fetuses without gastroschisis were used as controls. All fetuses were retrieved by cesarean section at day 135. Samples of the small intestine were stained with hematoxylin and eosin for histologic analysis of peel formation and serosal and muscular thickness. For ICC detection, immunohistochemistry using anti-CD117 (c-Kit) antibody was used.

Results

In all samples with exposure to amniotic fluid, peel formation and significantly decreased ICC were found. Complete coverage reduced peel formation and disorganization of ICC compared to uncovered animals almost to the level of controls.

Conclusions

Peel formation and ICC derangement were significantly reduced by prenatal coverage of gastroschisis. Moreover, this animal model mimics the histopathological bowel changes as seen in human gastroschisis and may, therefore, be used for further research on the pathophysiology and fetal therapy of this malformation.

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Acknowledgments

We would like to acknowledge the assistance and statistical support provided by Prof. Dr. Heiko Becher from the Department of Public Health, University of Heidelberg, Germany.

Disclosures

The research group received funding by Karl Storz Company in form of materials (Storz Camera Telepack®, Storz 3 mm and 5 mm laparoscopic instruments) and financial support by “Hamburg macht Kinder gesund e.V.” foundation. Apart from that the authors Thomas Krebs, Michael Boettcher, Hansjörg Schäfer, Georg Eschenburg, Katharina Wenke, Birgit Appl, Beate Roth, Thomas Andreas, Carla Schmitz, Rebecca Fahje, Birthe Jacobsen, Bastian Tiemann, Konrad Reinshagen, Kurt Hecher, Robert Bergholz have nothing to disclose.

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Authors and Affiliations

  1. Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Thomas Krebs, Michael Boettcher, Georg Eschenburg, Katharina Wenke, Birgit Appl, Beate Roth, Carla Schmitz, Rebecca Fahje, Birthe Jacobsen, Konrad Reinshagen & Robert Bergholz

  2. Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Hansjörg Schäfer

  3. Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Thomas Andreas & Kurt Hecher

  4. Department of Experimental Animal Research, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Bastian Tiemann

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  1. Thomas Krebs
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  2. Michael Boettcher
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  14. Kurt Hecher
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  15. Robert Bergholz
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Corresponding author

Correspondence to Michael Boettcher.

Additional information

Thomas Krebs and Michael Boettcher contributed equally to this manuscript.

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Krebs, T., Boettcher, M., Schäfer, H. et al. Gut inflammation and expression of ICC in a fetal lamb model of fetoscopic intervention for gastroschisis. Surg Endosc 28, 2437–2442 (2014). https://doi.org/10.1007/s00464-014-3494-x

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  • DOI: https://doi.org/10.1007/s00464-014-3494-x

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