It is widely recognized that throughout the ENM life cycle, the greatest risk for human exposure and subsequent health consequences begins with ENM inhalation, and is typically followed by systemic injuries. The prevalence of ENM covers an immense spectrum: surface coatings and additives in common consumer products (electronics, food, cosmetics), additives in industrial processes (advanced building materials, synthetic fuels), and components of clinical applications (diagnostics, drug delivery, implantable devices). However, the impact of maternal ENM on fetal health and/or epigenetic modification are poorly understood.Дespite the ubiquitous inclusion of engineered nanomaterials in widespread applications, and their projected proliferation in human endeavors, the consequences of maternal ENM inhalation on the developing fetus and their impacts on future health are at best, vague, yet they are increasingly becoming a health concern. For example, bisphenol A and air pollution have been shown to negatively impact fetal outcomes. Conceptually, this relationship is not novel, but applications of environmental toxicants to the maternal-fetal models are. While these studies have focused on the maternal development of a hostile gestational environment and subsequent reduction in fetal nutrients, fetal epigenetic modifications may also occur. We have reported that maternal ENM inhalation impairs the ability of uterine arterioles to properly dilate, and this impacts litter health in the form of pup weight, number and gender distribution as well as impaired microvascular function. Recently, maternal environmental toxicant exposures have become of prominent interest in relation to the impact of exposure on the fetal milieu and subsequent progeny health.

Maternal prenatal health challenges such as nutrient deficiency, undernourishment, gestational diabetes and hypertension have been linked to an elevated risk for postnatal cardiovascular diseases. The Barker Hypothesis, Developmental Origins of Health and Disease (DOHaD), and fetal programming, all explore the relationship between the health of the gestational environment and fetal development and how this predisposes to future disease or sensitivities. These results are the first evidence that maternal ENM inhalation impacts the fetal epigenome. Changes in normal physiology were linked with other tissues, including liver and kidneys. The most notable alterations in major biologic systems included immune adaptation and organismal growth. The results of the sequencing experiments provide initial evidence that significant epigenetic and transcriptomic changes occur in the cardiac tissue of maternal nano-TiO 2 exposed progeny. Ingenuity Pathway Analysis (IPA) was then used to identify pathways most modified by gestational ENM exposure. RNA from fetal hearts was purified and prepared for RNA sequencing and transcriptomic analysis. Following chromatin immunoprecipitation (ChIP), DNA fragments were sequenced. DNA was extracted and immunoprecipitated with modified chromatin marks histone 3 lysine 4 tri-methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3). Pregnant dams were exposed to nano-titanium dioxide (nano-TiO 2) aerosols (10вЂ‰В±вЂ‰0.5В mg/m 3) for 7-8В days (calculated, cumulative lung depositionвЂ‰=вЂ‰217вЂ‰В±вЂ‰1В Ојg) and on GD (gestational day) 20 fetal hearts were isolated. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications.

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