Cytotoxic effects of Shiga Toxin type 2 in Human Placenta

BURDET JULIANA; ZOTTA ELSA; MIGUEL MARIA S; DAMIANO ALICIA E; IBARRA CRISTINA

Los Cocos, Córdoba- Argentina

Simposio; III Latin-American Symposium on Maternal-Fetal Interaction and Placenta:Basic & Clinical Research; 2007

Placental Association of America

Infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolytic-Uremic Syndrome (HUS) became relevant in public health since it was considered as one of the most important emergent pathogens. STEC infection may be asymptomatic or begin with watery diarrhea associated with hemorrhagic colitis and HUS. The major virulence factor of STEC is Shiga toxin type 1 or 2 (Stx1, Stx2) although strains that express only Stx2 are highly prevalent. Up to now, it has not been established whether STEC infection affects pregnant women. The aim of this study was to evaluate the effects of Stx2 in explants from normal full-term human placenta. Explant viability was determined by water uptake and b-hCG level in the extracellular medium. Unidirectional flux of water was measured by the radiolabeled technique and b-hCG level by standard methods. Water uptake decreased whereas b-hCG increased in explants treated with 1ng/mL Stx2 for 1h. Stx2 was localized in the syncytiotrophoblast cells by immunohistochemistry studies where morphological alterations were observed by light microscopy. We also evaluated the effect of Stx2 in rats on late stage of pregnancy. Intraperitoneal Stx2 injection (3-4 mg/Kg) induced placental abruption, necrosis, intrauterine hemorrhage and fetal death in a dose-dependent fashion. Higher doses of Stx2 (6 mg/Kg) induced fetoplacental resorption, extensive necrosis areas and intrauterine hematoma with thrombosis. >Binding of Stx2 was observed in syncytiotrophoblast cells and blood vessels from fetuses. Although there are no reports of Stx-mediated fetal loss or damage in humans, we speculate that STEC infections during pregnancy could be detrimental to the fetus.