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This Article Full Text Full Text (PDF) All Versions of this Article: 79/3/510    most recent biolreprod.107.066373v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Allix, S. Articles by Bernex, F. PubMed PubMed Citation Articles by Allix, S. Articles by Bernex, F. Agricola Articles by Allix, S. Articles by Bernex, F.

Uterine Contractions Depend on KIT-Positive Interstitial Cells in the Mouse: Genetic and Pharmacological Evidence

Institut National de la Recherche Agronomique, UMR955 de Génétique Moléculaire et Cellulaire² and Unités de Physiologie-Thérapeuthique³ and d'Embryologie d'Histologie et d'Anatomie Pathologique,⁴ Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort, France

ABSTRACT

In the gastrointestinal tract, interstitial cells of Cajal (ICCs) generate a pacemaker activity. They produce electric slow waves that trigger and coordinate gut smooth muscle contractions. Interstitial cells of Cajal's slender shape is revealed by KIT immunostaining. Based on several features, including KIT expression and KIT dependence, ICC-like cells were identified in nongastrointestinal tissues. Here, we investigated in the mouse whether uterine contractions depend on ICC-like cells' activity. By labeling KIT-expressing cells, we found putative ICC-like cells in the uterus, observed as KIT-positive interstitial, long spindle-shaped cells with fine branched cytoplasm processes, distributed in muscular layers and in subepithelial connective tissue. We then checked the potential KIT dependence of ex vivo contractile activity of the uterus by combining genetic and pharmacological approaches, using the Kit^W-v hypomorphic mutation, and imatinib as a KIT noncompetitive inhibitor. We found a significant reduction in frequency of longitudinal uterine contractions in Kit^W-v/Kit^W-v compared with Kit^+/+ mice, whereas amplitude was unaffected. There was no difference in frequency or amplitude of circular uterine contractions between Kit^W-v/Kit^W-v and Kit^+/+ mice. Ex vivo treatment of Kit^+/+ uterine horns with imatinib resulted in a dose-dependent reduction of the frequency and amplitude of longitudinal myometrial contractions. Amplitude and frequency of circular contractions were unaffected in presence of imatinib. These concurrent results suggest that longitudinal contractions of the uterus depend on a KIT signaling pathway of ICC-like cells. The existence of ICC-like cells in the myometrium may enhance our understanding of uterine spontaneous contractile activity and suggest new approaches for treatment of uterine contractility disorders.

female reproductive tract, gene regulation, interstitial cells, signal transduction, uterus