Involvement of hypoxia and inflammation in early pregnancy loss mediated by Shiga toxin type 2

SACERDOTI FLAVIA; AMARAL MARÍA MARTA; FRANCHI ANA MARÍA; IBARRA CRISTINA

Mar del Plata

Simposio; VI SLIMP-V LASRI Meeting; 2015

Latin American Society for Maternal Fetal Interaction and Placenta

Symptomatic or asymptomatic Shiga toxin producing E. coli (STEC) infections during early pregnancy may cause maternal or fetal damage mediated by Shiga toxin type 2 (Stx2). We have previously demonstrated that Stx2 produces early pregnancy loss in rats. Objective: The aim of the present study was to elucidate the mechanisms responsible for early pregnancy loss in Sprague Dawley rats treated with Stx2. Methods: Sprague Dawley pregnant rats were intraperitoneally injected at day 8 of gestation with a sublethal dose (0.5 ng of Stx2/g of total body weight, 250 μl) of purified Stx2. Control rats were injected with the same volume of vehicle. Experimental and control rats were sacrificed 48 h post injection (day 10 of gestation) and blood and utero placental units were collected. Globotriaosylceramide (Gb3), Stx2 receptor, was detected by thin-layer chromatography and Stx2 was localized by immunohistochemistry. Hipoxia was evaluated using Hypoxyprobe-1 kit. Local VEGF expression was studied by Western blot. Inflammation was evaluated by leukocyte infiltration and both systemic and utero-placental TNF- expressions were evaluated by ELISA, 2 h post injection. Results: Our results demonstrate that Stx2 reaches the utero-placental unit where Gb3 is present. Stx2 injection triggers alterations in the utero-placental tissues and produces local hypoxia. However, no alterations in VEGF expression were detected in experimental rats compared to control. Decidual TNF- expression of Stx2 treated rats was increased. Conclusions: These results suggest that hypoxia and inflammation contribute to the early fetal loss produced by Stx2 and that VEGF is not early involved in this process. We propose that an alteration of the utero-placental microvasculature due to a direct cytotoxic effect of Stx2 is responsible for the hypoxia in the utero placental unit. Poor oxygen supply accompanied with the oxygen consumption and damage due to inflammation, could be responsible for the early pregnancy loss.