Nitric oxide is involved in the Shiga toxin mechanisms responsible for premature delivery of dead fetuses

BURDET JULIANA; ZOTTA ELSA; FRANCHI ANA MARÍA; IBARRA CRISTINA

Adelaide, Australia

Congreso; 15th Meeting of the International Federation of Placenta Associations.; 2009

IFPA

p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0cm 0cm 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; } Shiga toxin-producing Escherichia coli (STEC) infections could be one of the causes of fetal morbimortality in pregnant women. The main virulence factor of STEC is Shiga toxin type 1 or 2 (Stx1, Stx2). We have previously reported that intraperitoneal (i.p.) injection of culture supernatant from E. coli recombinant expressing Stx2 and containing lipopolysaccharide (LPS) in rats in the late stage of pregnancy induced premature delivery of dead fetuses. It has been reported that LPS may combine with Stx2 to facilitate vascular injury that may lead to a pathological cascade that involves the production of nitric oxide (NO). Objective Our aim was to evaluate if NO is involved the effects of Stx2 on pregnancy. Materials and methods Pregnant rats on days 14-16 of gestation were i.p. injected with culture supernatant from recombinant E. coli containing 0.4 µg/ml Stx2 and 30 ng/ml LPS.   A group of rats was previously injected with aminoguanidine (AG), an inducible NO synthase  (iNOS) inhibitor and the development of preterm labor was evaluated. Western blot analyses were performed to determine the iNOS expression in placentas from Stx2-treated and untreated rats. Results Stx2 and LPS induced fetal resorption, placental abruption, intrauterine hemorrhage and fetal death at 1-2 days post-injection. Pre-treatment of 24 h with AG caused significant reduction of Stx2 effects on the feto maternal unit but did not prevent the premature delivery of dead fetuses. Histological studies show no significant differences in placenta tissues from rats treated with AG and Stx2 compared with those treated only with AG or with controls. Western blot assays showed a higher expression of iNOS in placentas from Stx2-treated rats than in those previously treated with AG. Conclusions Our results suggest that NO is partially involved in the mechanisms of the premature delivery of dead fetuses caused by Stx2 and LPS.