Pathogens may impair reproduction in association or not with congenital infections. We have investigated the effect of acute infection with Trypanosoma cruzi, the protozoan agent of Chagas' disease in Latin America, on reproduction of mice. Although mating of infected mice occurred at a normal rate, 80% of them did not become gravid. In the few gravid infected mice, implantation numbers were as in uninfected control mice, but 28% of fetuses resorbed. Such infertility and early fetal losses were significantly associated with high maternal parasitemia. The remaining fetuses presented with reduced weights and all died later in gestation or within 48 hours after birth. Several organs of these fetuses were infiltrated by polynuclear cells and presented ischemic necrosis but did not harbor T. cruzi parasites, discarding congenital infection as the cause of mortality. However, surprisingly, the deciduas were massively invaded by T. cruzi parasites, harboring 125-fold more amastigotes than the maternal heart or other placental tissues. Parasites were significantly more numerous in the placentas of dead fetuses. In addition, placentas contained inflammatory infiltrates and displayed ischemic necrosis, fibrin deposits, and vascular thromboses. These results show that acute T. cruzi infection totally impairs reproduction in mice through inducing infertility or fetal-neonatal losses in association with placental parasite invasion and ischemic necrosis. Besides direct effects of infection on placentas and fetuses, poor pregnancy outcome might arise from disturbances in the complex biological processes tightly regulated by hormones and cytokines involved in mammal reproduction.3-5 Indeed, proinflammatory/type 1 cytokines such as tumor necrosis factor-␣ and interferon-␥, produced at high levels in response to some pathogens, have been shown to be harmful for pregnancy. 6,7 Information on the effect of infection with T. cruzi (the protozoa agent of Latin American Chagas' disease) on pregnancy is scarce though, and according to the endemic area, such infection affects 3 to 51% of pregnant women from which 2 to 10% congenitally transmit the parasite. 8,9 Some studies suggest that Chagas' disease might cause abortion or prematurity, whereas others fail to show such a relation.9 -11 Studies in experimental infection might reinforce our knowledge of maternofetal interactions in T. cruzi infection. Infertility and fetal growth retardation, associated or not with congenital infection, have been reported in chronic infection of mice. 12,13 In acute experimental infection, placental infection has been reported without congenital transmission, 14 despite the high circulating level of parasites, known to release proinflammatory molecules 15,16 and the systemic production of cytokines potentially deleterious for pregnancy. 17,18 The aim of the present work was to gain more insight into the relation between acute T. cruzi infection and gestation in mice, by studying the reproductive capacity, the pregnancy outcome, and the histopathology of...
