Maternal nanomaterial exposure: a double threat to maternal uterine health and fetal development?

Abstract

The potential applications associated with engineered nanomaterials (ENMs) are seemingly limitless, particularly in the broad disciplines of biomedical therapeutics and diagnostics, or ‘theranostics’ [1]. The National Nanotechnology Initiative has invested a considerable amount of resources, research and infrastructure for material development at dimensions less than 100 nm [2]. Materials manufactured at the nanoscale express unique properties and characteristics that differ from those of their larger counterparts of the same chemical composition. Furthermore, the toxicities and physiochemical properties of these ENMs are distinctly different, and thus are not well understood [3]. Moreover, novel ENMs and ENM properties are generated faster than their toxicities can be determined. Federal resources have been allocated to generate research and development of commercial products and medical technologies within the fields of drug delivery and imaging. To a lesser extent, these resources also support investigations into the toxicokinetics of these novel materials [2,4]. For good reason, most early nanotoxicology research has focused almost exclusively on pulmonary exposures within a young, healthy, male model. Our studies on micro-vascular dysfunction subsequent to ENM inhalation is of no exception. While this approach has yielded important descriptive and mechanistic information, the increased use of ENMs in novel biomedical and consumer products inevitably leads to increased occupational, environmental and domestic exposures to a variety of ENMs that are both intentional and unintentional. Perhaps some of the applications with the greatest potential to improve human health are those that require the intentional introduction of ENMs to the body. Such ENM exposure routes would no longer be limited to the lungs and would include ingestion, transdermal and injections (intravenous or other). Potential applications under development include drug delivery, high-resolution imaging, preventative measures (antioxidants) and implantable devices. The shear breadth of these applications mandates that we considerably widen our exposure models. The fetomaternal relationship during gestation is a unique, dynamic and complex physiological system. The term ‘milieu’, coined by Claude Bernard, or homeostatic environment is often used to describe different compartments, conditions and components associated with a given physiological function. At the outset, maternal health and homeostasis is paramount for a successful gestational outcome; therefore, uterine adaptation to pregnancy (e.g., growth and pressure regulation) or the uterine milieu must be first considered. Incorporated in the gestational uterine milieu is placental development, a transient organ with significant influence over fetal development. In addition to exchange of nutrients and wastes, the placenta serves as an endocrine organ to both the maternal and fetal circulations [5]. Lastly, the intrauterine environment where the fetus develops, or the fetal milieu, must be established and maintained to promote appropriate growth and development. Any dysfunction within the coordinated exchange of hormones, nutrients and wastes during gestation may lead to devastating fetal consequences. Therefore, regulation of maternal homeostasis and the fetal milieu are highly susceptible to a variety of external influences or exposures. Currently, our understanding of ENM exposure in these regards is quite poor. To date, few studies have explored the consequences of maternal ENM exposure during pregnancy [6–8]. Failure to recognize the consequences of ENM exposure during gestation may lead to untoward outcomes for generations. While it would be easy to label nanomaterial theranostics as contraindicated during pregnancy, the potential benefits within the field of obstetric theranostics may be immense. For example, applications of immediate interest to human health may include: fetal imaging, assessment of high-risk pregnancies and early pharmacological interventions. These promising advancements, while exciting and novel, can only reach their full potential if the toxicity of a given ENM, and its terms are first properly understood in all regards.