Cytotoxic effects of Shiga toxin tipo 2 in human placenta. I

BURDET J, ZOTTA E, MIGUEL MS, DAMIANO A AND IBARRA C.

Córdoba, Argentina

Simposio; III Lati-American Symposium Materno-Fetal Interaction & Placenta: From Basic to Clinical Research.; 2007

Infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolitic-Uremic Syndrome (HUS) became relevant as a public health since it was considered as one of the most important emergent patogen. STEC infection may be asymptomatic or begins with a 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 affect pregnant woman. The aim of this study was to evaluate the effects of Stx2 in explants from full term human normal placenta. Explant viability was determined by water uptake and ß-hCG level in the extracellular medium. Unidirectional flux of water was measured by radiolabeled technique and ß-hCG level by standard methods. Water uptake decreased whereas ß-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 evaluate the effect of Stx2 in rats on late stage of pregnancy. Intraperitoneal Stx2 injection (3-4 µg/Kg) induced placental abruption, necrosis, intrauterine hemorrhage and fetal death in a dose-dependent fashion. Higher doses of Stx2 (6 µg/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.