These findings suggest that the activation of TLRs in pregnancy causes not only preterm labor and pregnancy loss, but also pre-eclampsia. The fetus is not indifferent to a viral or bacterial infection, and the immunological responses by the selleck products maternal immune system or the placenta or fetal immune system may have important consequences on the normal development and survival of the fetus. In the following section, we will discuss some studies

related to the long-term effects of TLR ligation in the offspring. Administration of LPS to pregnant mice was shown to cause acute fetal cardiovascular depression,54 and inhibit structural development of the distal fetal mouse lung in a TLR4-dependent manner.66 Similarly, cerebral white matter damage, which is one of the biggest problems seen in preterm neonates because of its strong association with their lifetime adverse outcome, is also believed to be caused by TLR4 activation in the fetus.67 It is worthy to mention that low-dose LPS, which has no adverse effects on pregnancy outcome, dramatically increases brain injury to subsequent hypoxic–ischemic challenge in a newborn rat animal model.67 These findings XAV-939 price are compatible with clinical findings showing that maternal exposure to bacteria not only causes preterm labor, but also

contributes to long-term adverse outcome in the offspring such as cerebral white matter damage. Adverse effects of maternal TLR3 activations were also found in fetuses in various animal models. Maternal poly(I:C) or virus exposure cause marked behavioral changes in the offspring mouse,68 which is relevant to many epidemiological studies showing that maternal exposure to virus causes not only abortion or preterm selleck compound birth but also fetal schizophrenia and autism.69,70 Offspring of poly(I:C)-treated pregnant mice were shown to have less expression of brain-derived neurotrophic factor (BDNF), nerve

growth factor (NGF) and TNF-α in their placenta, liver/spleen and brain, which may represent a potential mechanism through which maternal viral infection increases a risk of such neurodevelopmental disorders.71 In contrast to the ‘adverse’ effects of maternal infection on fetus, there is a notion called ‘hygiene hypothesis’, that is, ‘adequate’ maternal microbial exposure has protective effects on neonatal allergic disease. Very recently, it was demonstrated that TLR system is also involved in this effect. Conrad et al.72 showed that an administration of non-pathogenic microbe Acinetobacter Iwoffii F78 to pregnant mice has a protective effect on postnatal asthma, and the effect was completely abolished in TLR2/3/4/7/9/null mice.