Abortion in AhR-knockout mice and fetomaternal immunity

Abstract

AhR knockout mice are not completely infertile; however, they do experience decreased litter sizes after repeated pregnancies. This study revealed that the decrease in the number of live births is partly due to fetal deaths leading to miscarriages. Interestingly, fetal mortality was found to be linked only to maternal AhR gene defects and not the fetal genotype. Furthermore, we observed no significant changes in litter sizes in allogenic pregnancy, where AhR-KO female mice were crossed with ICR male mice. The results indicated that the absence of AhR in the dams affected the expression of immune tolerance-related genes in both the placenta and fetus. Specifically, FoxP3 and indoleamine 2,3-dioxygenase-1 (IDO1) mRNA levels were lower in the placentas of AhR-KO dams than in those of wild-type dams. Moreover, there were elevated levels of IL-1β and IFN-γ mRNA in the placentas of the AhR-KO dams, which indicated increased inflammation. However, the mRNA expression levels of IL-6 and IDO1 were low despite the elevated mRNA levels of IL-1β and IFN-γ, which may be because AhR is directly involved in IL-6 and IDO1 transcription. These findings imply that in AhR-KO mice, fetal death may be attributed to the disturbance of fetal-maternal immune tolerance as a result of increased inflammation and reduced IDO1 and FoxP3 mRNA levels.