Contaminants of emerging concern in the fetal environment: unravelling the exposure and effects of endocrine disrupting compounds and micro(nano)plastics in utero

During pregnancy, women are exposed to a broad range of environmental contaminants that could reach the placenta and the fetus with maternal blood. These contaminants could influence placental functions, and fetal development and predispose the fetus to diseases later in life. The developing fetus is specifically susceptible to exposure to endocrine disrupting compounds (EDCs), a diverse group of chemicals that can interfere with hormonally-driven developmental processes. Moreover, there are new contaminants of emerging concern, such as micro- and nanoplastics (MNPs) that could reach the placenta and contribute to fetal exposure. Due to the great diversity of EDCs and MNPs in the environment and the obvious ethical limitations, studying these contaminants during pregnancy is extremely challenging and prenatal exposure is still not well characterized. This thesis aimed at addressing these knowledge gaps. Here, we developed, for the first time, a method that applied a combination of cell bioassays, state-of-the-art analytical techniques, and publicly available online databases and chemical screening tools, to identify a broad range of EDCs in human amniotic fluid. Moreover, we reviewed the state of the science of placental MNP research and human-relevant placental models. Furthermore, we investigated the possible uptake, transport and toxicity of pristine and environmentally relevant MNPs in trophoblast cells, key mediators of placental exchange, endocrine, and immune functions. This study reveals the presence of a large variety of EDCs in the direct fetal environment and suggests that diverse MNPs and compounds associated with them, are internalized and translocated in placental cells where they can induce subtle biological effects. Further studies are urgently needed to better understand the possible effects of these contaminants on pregnancy, fetal development and long-term health.