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-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.
Zhang
Jianhong
J
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei, Anhui 230027, China.
Wei
Haiming
H
Wu
Dongmei
D
Tian
Zhigang
Z
D000818:Animals; D001158:Arteries / Q000033:anatomy & histology; D003656:Decidua / Q000276:immunology* / Q000378:metabolism; D004717:Endometrium / Q000098:blood supply* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005313:Fetal Death; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011070:Poly I-C / Q000494:pharmacology*; D011247:Pregnancy; D011248:Pregnancy Complications; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000502:physiology
C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011070:Poly I-C