Tissue and Cell 40 (2008) 293–298 Morphological changes and EGF expression in the granular convoluted tubule cells of submandibular glands of Trypanosoma cruzi infected rats A. Moreira a , M.H. Napimoga a , B.B. Benatti a , G.A.B. Silva b , D.B. Rocha-Rodrigues a , J.T. Clemente-Napimoga a , Gustavo A. Vieira a , J.B. Alves a,∗ a Laboratory of Molecular Biology, University of Uberaba, Av. Nene Sabino, 1801, Aeroporto, CEP 38.055-500 Uberaba, MG, Brazil b Institute of Biological Science, Federal University of Minas Gerais, Brazil Received 7 November 2007; received in revised form 5 February 2008; accepted 20 February 2008 Available online 10 April 2008 Abstract We have previously demonstrated in rats that Chagas’ disease affects the salivary glands, by promoting an enlargement of the submandibular gland. In order to further investigate possible functional alterations on infected submandibular glands, the objective of the present study was to analyze epidermal growth factor (EGF) expression on rat submandibular glands during Trypanosoma cruzi infection. Results demonstrated that infected rats presented lower levels of testosterone, and morphological changes in the granular convoluted tubule (GCT) cells of the submandibular glands, along with acinar enlargement and delayed ductal maturation at the developing granular ducts. Immunohistochemistry analysis additionally showed that only few cells immunolabelled with anti-EGF on infected rats during the acute phase of Chagas’ disease, while after 64 and 90 days (chronic phase) of infection, EGF expression was similar to non-infected rats. The present findings suggest that at the acute phase of Chagas’ disease, lower levels of testosterone may lead to a delayed maturation of GCT, which positively correlates with decreased EGF production by submandibular glands cells. © 2008 Elsevier Ltd. All rights reserved. Keywords: Submandibular gland; Trypanosoma cruzi; Epidermal growth factor; Chagas’ disease 1. Introduction Chagas’ disease is caused by the flagellate protozoon Trypanosoma cruzi, which is transmitted by the feces of blood-sucking insect vectors (Triatoma). The parasite plays a fundamental role by inducing immunopathology and tissue damage in organs such as the heart, esophagus, and colon by sequentially inducing inflammatory responses, cellular lesions, and fibrosis (Teixeira et al., 2002). Besides the involvement of the cardiovascular and diges- tive system, we have previously demonstrated that this disease also affects the salivary glands, by promoting an enlargement of the submandibular gland in rats (Alves and Abbreviations: EGF, epidermal growth factor; NGF, nerve growth factor; GCT, granular convoluted tubule. ∗ Corresponding author. Tel.: +55 31 9984 70 76; fax: +55 34 3314 89 10. E-mail address: propg.pr@uniube.br (J.B. Alves). Machado, 1980). This observation was more evident dur- ing the acute phase of experimental Chagas’ disease, in which the absence of appreciable inflammatory process in the submandibular glands of T. cruzi infected rats induced a severe reduction in sympathetic (Machado et al., 1984) and parasympathetic innervation (Alves and Machado, 1984). At the histological level, the main changes observed were accel- erated acinar development and delayed ductal maturation, characteristics that were more evident in the developing gran- ular ducts (Alves and Machado, 1980). On the other hand, during the chronic phase of experimental Chagas’ disease the acini returned to its normal size and the granular duct showed complete pattern recuperation (Alves et al., 1995). However, the underlying mechanisms are still unknown. It has been demonstrated that some factors produced by submandibular glands may stimulate lymphocyte prolifera- tion, affect the weight of the thymus, spleen and lymph nodes and induce immunosuppression in several in vivo animal 0040-8166/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tice.2008.02.004