Immunotoxicological disruption of pregnancy as a new research area in immunotoxicology.

Abstract

Immune mechanisms associated with normal pregnancy have only been being substantively investigated since the early 1990s. In parallel with the progress in that area of research, in the past few years it has become increasingly clear that several xenobiotics - including a variety of environmental chemicals, pharmaceuticals, and metals are considered to be both generally immunotoxic and specifically able to affect pregnancy. Among these, there is intense interest regarding potential effects from synthetic cannabinoids, immune checkpoint inhibitors, nanometals, and microplastics, with immunotoxic events that impact on pregnancy being shown for these agents. For instance, phytocannabinoids have been shown to interfere with reproduction in mice through effects on the endocannabinoid system. Because of effects of immune enhancement, as a requirement for regulatory submission, co-inhibitory immune checkpoint molecule inhibitors were also evaluated for effects on pregnancy. Similarly, because of increasing use and concerns about incidental environmental exposures, nanometals, and micro-plastics have also been examined for effects. Several studies in humans or mice showed that exposures to each during gestation increased the risk/rate of fetal loss, in part, by disruption of the placenta-associated immune system. Furthermore, signaling by endogenous danger molecules and/or impairment of physiological intercellular mediators may have contributed to the pregnancy loss. As there are clearly a variety of immunotoxic effects that can impact on a pregnancy, this review attempts to briefly introduce immune mechanisms associated with pregnancy as well as reasons for its loss, and proposes that 'immunotoxicological disruption of pregnancy' be accepted as a new research area in immunotoxicology.