Congenital Chagas disease, a neglected tropical disease, endemic in Latin America, is associated with premature labor and miscarriage. During vertical transmission the parasite Trypanosoma cruzi (T. cruzi) crosses the placental barrier. However, the exact mechanism of the placental infection remains unclear. We review the congenital transmission of T. cruzi, particularly the role of possible local placental factors that contribute to the vertical transmission of the parasite. Additionally, we analyze the different methods available for studying the congenital transmission of the parasite. In that context, the ex vivo infection with T. cruzi trypomastigotes of human placental chorionic villi constitutes an excellent tool for studying parasite infection strategies as well as possible local antiparasitic mechanisms. 1. Introduction Chagas disease was first described by the Brazilian physician, Carlos Chagas, in 1909. He identified the causal agent, the protozoan Trypanosoma cruzi (T. cruzi), the vectorial transmission and insect reservoirs as well as the clinical signs and symptoms. In other words, he described the complete cycle of the disease and suggested the possibility of congenital transmission [1]. In the human villous hemochorial placenta, fetal and maternal tissues are separated by a fetal epithelium (the trophoblast). Within the villous placenta, a single multinucleated cell layer (syncytiotrophoblast) contacts maternal blood within the intervillous space. Beneath the syncytiotrophoblast reside replicating progenitors (cytotrophoblast) that are separated by a basal lamina from the connective tissue of villous stroma containing vascular endothelium, fibroblasts, and macrophages. The syncytiotrophoblast forms a surface of about 12？m2 that contacts maternal blood. Therefore, in case of women with Chagas disease, the parasite has the opportunity to interact with a large cellular surface. The mechanism of T. cruzi congenital transmission can be studied in different ways. One of the possible ways is through the dual placental perfusion system. The dual perfusion that simulates the maternal and fetal circulation could be an excellent method to study the mechanism of the transmission of the parasite [2]. However, this method requires complex equipment and very experienced users. Another possibility is the ex vivo infection of human chorionic villi explants, in which samples of placental tissue (chorionic villi) can be challenged in vitro with T. cruzi or other pathogens. This system is preferred to analyze the process of infection of the placental
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