The objective of this study was to examine the expression of Toll-like receptor (TLR) 3 at the maternal-fetal interface and determine whether exposure to TLR3 agonist would induce an innate immune response and trigger pregnancy loss. To address this, abortion-prone male DBA/2J mated-CBA/J female mice were given polyinosinic-polycytidylic acid (poly I:C; 10 microg/g body weight, i.p.) or PBS at gestation day (gd) 6.5. All implantation sites appeared viable at gd 7.5 when endometrium was dissected for immunohistological examination. It was noted that poly I:C treatment increased fetal losses to 40.2+/-1.7% at midgestation stage compared with control animals (11.0+/-3.0%). It was observed also that the ratio of vessel to lumen area significantly increased at gd 10.5 and gd 12.5 after poly I:C treatment, indicating that the spiral artery (SA) modification was impaired. Meanwhile, 24h after poly I:C injection, expression of TLR3 was markedly elevated within decidua basalis (DB), and endometrial TNF-alpha increased 2.7-fold but IFN-gamma remained unchanged in homogenized endometrium. These results suggest that enhanced TNF-alpha expression in endometrial stroma may play a critical role in inflammatory factor production and impairment of uterine spiral artery remodeling in the pregnancy failure of CBA x DBA/2 mating.