Expression of Allograft Inflammatory Factor‐1 in Mouse Uterus and Poly (I:C)‐induced Fetal Resorption

Abstract

Problem: To investigate whether the allograft inflammatory factor‐1 (AIF‐1) is expressed and plays a role in the reproductive system. Method of study: AIF‐1 expression was examined in uteri of non‐pregnant and pregnant mice by Northern blot analysis, RT‐PCR and immunohistochemistry. Results: The expression of AIF‐1 varied during the estrous cycle with a peak at estrus. After the insemination, the expression of AIF‐1 mRNA diminished gradually and again increased in the pre‐implantation or implantation period in allogeneic or syngeneic pregnancy, respectively. Enhanced expressions of AIF‐1, tumor necrosis factor‐α (TNF‐α) and nitric oxide synthase 2 (NOS2) mRNA were observed in the embryos of resorption‐prone pregnancy injected with poly(I:C). Conclusions: This study demonstrated for the first time that AIF‐1 was expressed in uterus. The expression level was associated with the population size of macrophage and varied during the estrous cycle and the pregnancy period. The augmented expression of AIF‐1 with concomitant expressions of TNF‐α and NOS2 mRNA in poly(I:C)‐injected mice suggests a correlation between AIF‐1 production and fetal resorption.

Murine CD200+CK7+ trophoblasts in a poly (I:C)-induced embryo resorption model

“…In abortionprone CBA/J £ DBA/2 mating combinations, the natural resorption rate (RR) of about 20 -40% could be boosted to 60% if the females were injected with poly (I:C) (Shimada et al 2003).…”

“…In another design, the CD200 þ CK7 þ percentage was detected in short-term cultured trophoblast cells in the presence or absence of poly (I:C) to evaluate its potential effect on CD200 expression. In addition, the contribution pattern of the CD200 molecule was also investigated with histological and histocytochemical examination in the embryonic units, defined as individual embryos together with placenta and embracing uterine tissue (Shimada et al 2003).…”

TLR3-Involved Modulation of Pregnancy Tolerance in Double-Stranded RNA-Stimulated NOD/SCID Mice

“…In addition, the significance of TLR3 interaction with dsRNA remains unclear in the mechanisms of poly(I:C)-induced embryo rejection. Some investigators suggest that inflammatory factors may be involved, which are secreted after the activation of macrophages, NK cells, or other cell populations (13). It is believed that cytokine imbalance and immune dysfunction are implicated in problems such as spontaneous abortion and endometriosis, but the trigger of these cytokine imbalances is not known (22,23).…”

“…Polyinosinic-polycytidylic acid (poly(I:C)) 3 is a synthetic dsRNA capable of boosting the resorption rate of embryos (RR) in murine models (13). Although dsRNA is known as a virus-specific signature and a ligand for TLR3, largely uncharacterized multiple pathways associate with dsRNA-mediated embryo resorption.…”

“…injection of poly(I:C) (gamma-irradiated, catalog no. P0913; Sigma-Aldrich, St. Louis, MO) at a dosage of 200 g/20 g of body weight in a volume of 200 l at gestational days 6.5 and 7.5, respectively (13,14). The pregnant mice were killed at day 8.5, 12.5, 16.5, or 20.5 of gestation, and RR was calculated as follows: RR (%) ϭ (number of resorbed embryo)/(number of total embryo) ϫ 100 (14).…”