Micro- and nanoplastic inhalation during pregnancy: Impacts on uteroplacental function and offspring health

Millions of tons of plastics are produced annually. Plastic products have become a staple in everyday life because of their low cost and high durability. However, the high production, popularity amongst consumers, and versality of plastic materials has led to a global contamination issue. Micro- and nanoplastics (MNPs) are a far-reaching, emerging environmental contaminant that has been identified in indoor air, ambient air, and some of the most remote places on earth. These particles are generated from the mechanical, thermal, and oxidative breakdown of large plastics materials. Particles of the micro (>100 nm and < 5 mm) and nano (<100 nm) size range easily become aerosolized and inhaled by humans. Additionally, particles in the micro- and nano-size range can reach the deep lung, where they may translocation biological barriers, enter systemic circulation, and interact with tissues. Detection of MNPs in the human placenta and newborn meconium has raised concerns as to whether these particles have an impact on human development during pregnancy. The effects of maternal MNP exposure on the health of pregnancy has only recently began to be addressed. Paramount to the health of the pregnancy is uteroplacental function and development. As described by the Developmental Origins of Health and Disease hypothesis popularized by David Barker, a suboptimal intrauterine environment can program adaptations in offspring that contribute to the development of cardiovascular disease in later life. Therefore, the purpose of this dissertation was to characterize how MNP inhalation in rats impacts uteroplacental function and elucidate the consequences of gestational MNP exposure to offspring health. Following repeated maternal inhalation of polyamide-12 MNP at a concentration of 10 mg/m3 throughout the rat pregnancy, it was determined that dilation of the maternal vasculature in the uterus was impaired which is a necessary maternal adaptation to support pregnancy. Further examinations revealed that the exposure resulted in decreased bioavailability of the nitric oxide (NO), a key vasodilator, particularly during pregnancy. Subsequent studies demonstrated that maternal MNP inhalation reduced remodeling of the maternal vessels that supply oxygen and nutrients for fetal development. Furthermore, maternal MNP inhalation reduced the surface area of maternal and fetal blood sinusoids, which indicates the fetal circulation has less access to oxygen and nutrients in the maternal blood due to the exposure. Final studies capitalized on the observed aberrations in uteroplacental function by identifying prenatal cardiovascular dysfunction and long-term cardiovascular deficits in female offspring of dams exposed to MNPs during pregnancy. Together this research reveals that following maternal MNP inhalation during pregnancy, uteroplacental function and morphology assumes a phenotype that decreases fetal receipt of vital nutrients during development, resulting in adverse outcomes in adult offspring rats. This dissertation provides novel insights into the mechanistic targets of MNPs during pregnancy in the rat. Overall, this work advances the fields of environmental, developmental, and cardiovascular toxicology.