Placental translocation and toxicity of environmentally relevant nanoplastics

PROJECT SUMMARY Nanoplastics are plastic particles less than 1 micron that form from the physical breakdown of environmental and household plastic in the environment. Nanoplastics are persistent in the environment and are continuously formed, leading to ubiquitous exposure in humans and wildlife. Existing evidence from human and animal studies suggests that nanoplastics are present in human organs and may disrupt health, particularly during sensitive windows of development. One challenge of current nanoplastics research is that most researchers have defaulted to using pristine polystyrene spheres, but these do not resemble particles found in the environment or human tissues, such as the placenta. Gestation is a sensitive period of development that is particularly sensitive to disruption by environmental factors. Dysregulated placental development and function are key determinants in pregnancy complications including intrauterine growth restriction and preeclampsia. The goal of this proposal is to study the placental toxicity of environmentally relevant nanoplastics using a combination of in vivo rodent and cutting-edge in vitro human placental organoid models. In addition, we aim to directly compare the behavior and effects of environmentally relevant model nanoplastics with polystyrene spheres to guide future research in the field. In the first aim of this study, we will investigate the distribution of nanoplastics in mouse placenta following prenatal exposure to understand how particle characteristics such as shape and weathering state impact uptake and accumulation. In the second aim, we will compare the placenta toxicity of nanoplastics of various physicochemical properties with polystyrene spheres to identify how particle characteristics impact toxicity, specifically focusing on the link between disrupted tissue architecture and estrogen signaling. When completed, this grant will provide timely, important public health information on the risks of plastic waste accumulation and weathering as well as insights into the contributions of environmental exposures to pregnancy conditions such as intrauterine growth restriction and preeclampsia.