ABSTRACT
Congenital transmission of Toxoplasma gondii may occur if the mother gets infected for the first time while pregnant. The risk of mother-to-child transmission depends on the gestation trimester at infection, being lowest in the first and highest in the last. Conversely, fetal damage is frequent and more severe at the beginning of pregnancy. The objective of this study was to evaluate congenital transmission and pathological aspects in the placenta and the fetus using a mouse model of congenital infection of the second gestation third. Forty-five female BALB/c mice were infected intravenously with 2.5-10.0 × 10(6) tachyzoites of the ME49 strain at middle gestation. Samples of maternal spleen and fetal/placental units were taken 72 h later. We determined parasite load and vertical transmission by qPCR, as well as damage macroscopically and by histopathology. With the lowest dose, 18% of the fetuses were infected. Also, 40% of fetuses/litter were altered, while this value was 10% in the control group (P < 0.05). These results are similar to those described in humans in terms of vertical transmission and fetal damage during the second third of gestation. The maternal spleen had 10-1000 times more tachyzoites than the placenta, and the later retained 90-99% of the parasites that could reach the fetus. Nevertheless, we found resorptions, abortions or fetal tissue damage in the presence but also in the absence of parasites. Our data indicate a strong protective effect of maternal organs and the placenta against fetal infection, but extensive damage of the later may led to resorption or abortion without vertical transmission.
Subject(s)
Fetus/parasitology , Infectious Disease Transmission, Vertical , Placenta/parasitology , Pregnancy Complications, Parasitic/parasitology , Toxoplasmosis, Animal/congenital , Animals , DNA-Binding Proteins/genetics , Disease Models, Animal , Embryo Loss/parasitology , Female , Fetus/pathology , Hemorrhage , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Necrosis , Parasite Load , Placenta/pathology , Pregnancy , Pregnancy Complications, Parasitic/pathology , Specific Pathogen-Free Organisms , Spleen/parasitology , Thrombosis , Toxoplasmosis, Animal/pathology , Toxoplasmosis, Animal/transmissionABSTRACT
PROBLEM: Bovine tritrichomonosis is a sexually transmitted disease caused by Tritrichomonas foetus, characterized by conceptus loss. We developed a mouse model of tritrichomonosis to study the mechanisms involved in the embryonic death. We hypothesized that embryonic death may be due to an exacerbated maternal response to the pathogen that then affects embryo development. METHOD OF STUDY: We infected BALB/c mice with Tritrichomonas foetus and paired them after confirming active infection. We studied the expression of pro- and anti-inflammatory cytokines, markers for T regulatory and T helper 17 cells as well as haem-oxygenase-1 expression in uterine tissue by real-time RT-PCR. RESULTS: As expected, TNF-α was augmented in infected animals. IL-10 and IL-4 were also up-regulated. Treg-associated genes were higher expressed in uteri of infected group. In mice that have lost their conceptus after the infection, haem-oxygenase-1 (HO-1) mRNA levels were strongly decreased, while RORγt mRNA, a reliable marker for Th17, was augmented in uterus. CONCLUSION: A T effector response of type 1 and 17 may be involved in tritrichomonosis-related embryonic death. This alters protective mechanisms as HO-1. Increased regulatory T cells may facilitate embryonic death by promoting the persistence of infection.