Authors S. WELLENS (1), A. ACCARIE (2), J. TOTH (1), L. WAUTERS (1), R. FARRÉ (1), J. TACK (1), T. VANUYTSEL (1) / [1] KU Leuven, , Belgium, Translational Research Center for Gastrointestinal Disorders (TARGID), [2] Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Leuven, Belgium, Clinical and Experimental Medicine
Introduction Functional gastro-intestinal disorders (FGID) are twice as prevalent in women than in men. Susceptibility to anxiety and stress, both more prevalent in women, are reported as predisposing factors to develop FGID. The Wistar Kyoto (WKY) rat is an anxiety-sensitive strain compared to the more resistant Sprague Dawley (SD).
Aim We aimed to investigate the intestinal phenotype in male and female WKY and SD rats and evaluate the gender difference in both strains to further unravel the complex interplay between sex and anxiety in the onset of visceral hypersensitivity, hyperpermeability and local immune cell infiltration
Methods Male and female WKY and SD (n=7/group) were tested for anxiety behavior by using the marble burying test and for colonic sensitivity at d90 by measuring the visceromotor response (VMR) to isobaric (from 15 to 60 mmHg) distensions. Intestinal and colonic permeability, mast cell and eosinophil infiltration were measured with Ussing chamber studies, Chromotrope2R staining and Mast Cell Protease type 2 immunostaining respectively.
Results For both genders, WKY showed an increased visceromotor response to colorectal distension (Fig.1) compared to SD which was associated with an increased anxiety-like behavior in females (8.5±1.3 vs 13.11±0.9 marbles buried, p<0.03) and males (9±1 vs 12.44±0.9, p<0.05). Female WKY displayed an increased paracellular permeability in the jejunum (197.9±55.64 vs 379±48.14 pmol/cm², p<0.05) associated with a trend to increased eosinophil infiltration (577.9±51.54 vs 732.7±57.58/mm², p=0.09) while male WKY tended to have increased transcellular (0.10±0.019 vs 0.18±0.03 µg/ml, p=0.07) and paracellular (170.3±23.34 vs 319±69.35pmol/cm², p=0.09) permeability. In both strains, females displayed an increased visceromotor response to colorectal distension (Fig.1) compared to males while the anxiety behavior was similar. For the WKY, females presented an increased immune cell infiltration characterized by eosinophils in both the colon (132.9±19.34 vs 407±44.10/mm², p<0.05) and jejunum (375.9±30.4 vs 732.7±57.58, p<0.05/mm²) while for the female SD, an increased transcellular permeability to horseradish peroxidase was found (0.1±0.019 vs 0.2±0.04 µg/ml p<0.05).
Conclusions Our results highlight that the genetic background and the sensibility to disorders such as anxiety, modify the sex-difference in the gastrointestinal phenotype. These observations further confirm the necessity to consider not only gender, but also the genetic background of the animals in the study of FGID pathophysiology.
