Development and Validation of a Minimally Invasive Transuterine Experimental Model of Gastroschisis.

Abstract

INTRODUCTION: Perinatal management of gastroschisis remains a subject of substantial research. Current models, including teratogenic, genetic, and surgical approaches, often fail to accurately replicate gastroschisis, exhibiting limitations such as inaccurate phenotyping, low success rates, high mortality, lack of scientific validation, and significant technical challenges. Refined disease models are essential for improving the understanding of GS. This study seeks to develop and validate a minimally invasive transuterine experimental model of GS that overcomes these existing constraints to advance gastroschisis research. METHODS: A gastroschisis model was surgically created in rat fetuses at E17 (n&#xa0;=&#xa0;51 fetuses from n&#xa0;=&#xa0;13&#xa0;dams). Intestines were harvested at term and divided into herniated gastroschisis (GS-H), intra-abdominal gastroschisis (GS-I), and control (Co) groups. Morphometric analysis, histopathological examination, immunohistochemistry for interstitial cells of Cajal (ICC), double immunofluorescence for ICC and mast cells, TUNEL assay for apoptotic cells, and multiplex cytokine assay were performed to assess intestinal architecture, inflammation, ICC network, apoptosis, and cytokine levels across studied groups. RESULTS: Histology from GS intestines revealed subchronic inflammation, peel formation, and architectural disruption. Herniated intestines exhibited a significantly increased weight/length ratio and thicker outer layers (p&#xa0;<&#xa0;0.001) compared with control intestines. Herniated intestines had elevated inflammatory cytokine levels (GS-H vs GS-I and Co, p&#xa0;<&#xa0;0.05 for G-CSF, GM-CSF, IL-12p70, IL-1beta) and increased apoptotic activity. CONCLUSIONS: We developed and validated a new surgical model of GS that offers improved survival and feasibility. The key morphological changes and molecular markers observed in this experimental model resemble human gastroschisis.