Maternal/fetal mortality and fetal growth restriction: role of nitric oxide and virulence factors in intrauterine infection in rats

Objective The mechanism of infection-related deaths of pregnant rats and intrauterine growth restriction are not understood. We assessed whether nitric oxide (NO) has differential effects on infection with Escherichia coli Dr/Afa mutants that lack either AfaE or AfaD invasins. Study Design Sprague-Dawley rats were infected intrauterinally with the clinical strain of E coli AfaE+ D+ or 1 of its isogenic mutants in the presence or absence of the NO synthesis inhibitor NG -nitro-L-arginine methyl ester (L-NAME). Maternal/fetal mortality rates, fetoplacental weight, and infection rates were evaluated. Results Maternal and/or fetal death was associated with the presence of at least 1 virulence factor (AfaE+ D+ >AfaE+ D− >AfaE− D+ ) and was increased by L-NAME treatment. The fetal and placental weights were lower than controls and were further reduced by L-NAME treatment. Conclusion These results demonstrate that NO enhanced AfaE- and AfaD-mediated virulence and plays an important role in Dr/Afa+ E coli gestational tropism.