Vertical transmission and pathological findings in the mother, the placenta and the offspring, during first and last thirds of gestation in a mouse model of congenital toxoplasmosis.

We performed a study of congenital toxoplasmosis of the first and third gestation periods in mice, and determined its effects on the embryos/fetuses, the placentae and the maternal organs. We infected pregnant BALB/c mice by i.v. injection of 2.5--10.0 × 106 tachyzoites of the ME49 T. gondii strain and euthanized them 72 h later. The tissues were analyzed by histopathology, immunohistochemistry and parasite-specific qPCR. Infections with the lowest dose induced remarkably different changes in the two thirds: a) all doses diminished the number of products/litter, the lowest dose only by 14%; but most embryos still visible were degenerated in the case of the first period, while the fetuses of the last third were perfectly preserved; b) the transmission rate in the first third was relatively high, but with a very low parasite burden; c) with the lowest dose, strong vascular changes (congestion, thrombosis and hemorrhage) predominated in the placentas of the first period, while they were absent in the last third; d) necrosis caused by T. gondii to maternal organs was much stronger during the last gestation period than in the first. Our results suggest that the vascular alterations at the placenta of the first third of pregnancy prevent embryo from large parasite burden, but provoke its death by starvation. In the last gestation period, there was poor control of parasite dissemination to the placenta and the fetus, but there was greater capacity of the product to defend itself from T. gondii.

Is Toxoplasma gondii type related to clinical outcome in human congenital infection? Systematic and critical review.

In human congenital toxoplasmosis the effects of parasite burden and pregnancy time at infection on clinical outcome are well known, but there is controversy regarding the role of Toxoplasma gondii type. Through a systematic review of the literature, we aimed to discern if T. gondii type has a role on clinical outcome in human congenital toxoplasmosis. We built up a database of congenital toxoplasmosis from reports of cases, case series and screening-based cohorts, which had information about parasite type, gestation time at maternal infection and/or clinical outcome in the product. Then, we obtained frequencies for loci used to genotype geographical origin of cases and types found. Also, odds ratios were calculated for association between time of maternal infection or parasite type on outcome. Type II parasites were the most common in Europe, Asia and Africa, while in America there were mainly atypical strains. More newborns with clinical problems were born from mothers infected during the first half of gestation than from those acquiring the parasite after week 24, regardless of parasite genotype (92.9 vs. 16.1 %, OR = 67.9, CI95 25.4-181.6). Type I and atypical parasites were associated with clinical problems as opposed to types II and III, regardless of pregnancy period at infection (86.9 vs. 72.9 %, OR = 2.47, CI95 1.1-5.4). A significant and remarkable tendency of type I parasites to be present during early pregnancy was also observed (94.4 vs. 5.6 %, P < 0.009). In addition to parasite burden and period of gestation, T. gondii genotype seems involved in CT clinical outcome.

Mouse model of congenital infection with a non-virulent Toxoplasma gondii strain: Vertical transmission, "sterile" fetal damage, or both?

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.

The neuroimmunoendocrine network in the complex host-parasite relationship during murine cysticercosis.

We review here the role that sex steroids play in experimental intraperitoneal Taenia crassiceps cysticercosis of male and female BalbC/AnN mice. Briefly, estrogens favour and androgens hinder the reproduction of cysticerci by at least two main mechanisms: 1) through estradiol tilting the TH2/TH1 immune system balance towards parasite-permissive TH2 response,which is IL-6 dependent mediating P450-aromatase over expression, shunting testosterone towards estradiol and thus creating a positive feed-back loop which progressively favours TH2 response, blocking in turns TH1 and furthers parasite growth; and 2) estrogens and androgens acting directly upon the cysticercus reproductive system, favoring or hindering, respectively, its asexual reproduction. Later infection, when parasite loads are for milliars, male mice become estrogenized, deandrogenized and diminish their copulative, aggressive and social behaviors in association with P450-aromatase testis overexpression. Changes in c-fos expression in different areas of the infected mice brain point to the additional connection of the central nervous system with the infection driven events, which senses and perhaps reacts to infection with behavioral changes. This complex immune-neuro-endocrine network management of parasite loads in murine cysticercosis, and its physiological and behavioral consequences upon the host, may be operative in other infections of mammals. Such complexity may also help to explain the often conflicting results, observed between infections with respect to the role of the host sex, and hints to other avenues of research and strategies for their treatment and control.

Gonadectomy and progesterone treatment induce protection in murine cysticercosis.

The effects of progesterone on castrated mice of both sexes infected with Taenia crassiceps cysticerci were studied. Gonadectomy and treatment with progesterone before infection decreased parasite loads by 100% compared with intact uninfected mice. mRNA levels of IFN-gamma and IL-2 (typically associated to Th1-like profiles) were markedly decreased in infected gonadectomized (Gx) mice, whereas progesterone treatment of infected Gx mice did not affected its expression. mRNA levels of IL-4, and IL-10 (typically associated with Th2-like profiles) were reduced by gonadectomy, whereas restitution with progesterone did not affected this pattern in infected Gx progesterone-treated mice. Infection markedly induced expression of progesterone receptor isoform A in splenocytes of Gx mice (5-fold), whereas isoform B had no changes. Progesterone metabolism to dehydroepiandrosterone (DHEA) in Gx animals was increased 3-fold only in infected progesterone-treated uninfecteds of both sexes, but was not detectable in infected Gx progesterone-treated mice. Conversely, DHEA levels increased 100-fold in infected Gx progesterone-treated mice. However, androgen receptor expression in splenocytes of male mice showed a reduction by gonadectomy, and by infection, whereas in females AR expression showed no changes in the different mouse groups. These results suggest that progesterone, through its metabolism to DHEA, negatively affects the establishment, growth, and reproduction of Taenia crassiceps, by a mechanism that does not implicate a classic genomic pathway involving a nuclear androgen receptor.