TLR4 and placental insufficiency: Additionally, antiphospholipid antibodies localize in the placenta, causing associated inflammatory responses, especially complement activation and neutrophil recruitment, having direct implications in the genesis of placental insufficiency [20]. Furthermore, in vitro studies with human extravillous trophoblasts from the first trimester have shown that anti-β2GPI antibodies trigger the production of pro-inflammatory cytokines and chemokines (particularly IL-1, IL-7, and IL-8) through the Toll-like receptor 4 (TLR4).