Figure 2.

Hypothesis. Various forms of intrauterine stress elicit the mobilization of DAMPs which direct fetal and placental responses through activation of TLRs of the innate immune system. TLR activation leads to the expression of genes involved in inflammation, cellular differentiation, proliferation and survival. TLR activation can account for all of the reported changes underlying programmed vascular dysfunction and hypertension, including vasoconstriction, intima hyperplasia, altered extracellular matrix (ECM) remodeling and altered phenotypic modulation of vascular smooth muscle cells (VSMC). Reactive oxygen species (ROS) are both products and inducers of TLR signaling and thus continual TLR activation during prolonged intrauterine stress may propagate the cycle of oxidative stress observed in IUGR fetuses and thereby exacerbate deleterious developmental aberrations.