Toll-like receptor 3 agonist induces impairment of uterine vascular remodeling and fetal losses in CBA x DBA/2 mice

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-polyeytidylic acid (poly I:C; 10 mu g/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 LC 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, 24 h after poly LC 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. (C) 2006 Elsevier Ireland Ltd. All rights reserved.