There is a strong association between infection and prematurity; however, the 
underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular 
pattern recognition receptors that are activated by bacterial peptides and 
mediate innate immunity. We previously demonstrated that human first-trimester 
trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. 
This study sought to determine the expression and function of Nod1 and Nod2 in 
third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 
activation on pregnancy outcome. Human term placental tissues and isolated term 
trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, 
bacterial γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast 
cultures induced a proinflammatory cytokine profile, characterized by elevated 
levels of secreted IL-6, GRO-α, and MCP-1, when compared with the control. 
However, these cytokines were not upregulated in response to Nod2 stimulation 
with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant 
C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. 
iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, 
altered the cytokine profile at the maternal-fetal interface, and induced fetal 
inflammation. Thus, functional Nod1 is expressed by trophoblast cells across 
gestation and may have a role in mediating infection-associated inflammation and 
prematurity. This study demonstrates that pattern recognition receptors, other 
than the TLRs, may be implicated or involved in infection-associated preterm 
labor.