EFFECTS OF GESTATIONAL DIPHENYLARSINIC ACID EXPOSURE ON BIRTH OUTCOMES AND NANOPLASTIC BIODISTRIBUTION IN THE NEONATAL BRAIN

Nanoplastics (NPs) are increasingly detected in biological samples and show particularly high levels in the brain, yet the mechanisms enabling this accumulation remain unresolved. Our previous work demonstrated that 50 nm NPs can enter the neonatal mouse brain, motivating further investigation into factors that may influence early-life NP brain access. Diphenylarsinic acid (DPAA), an organic arsenic compound historically detected in contaminated well water in Japan, exhibits neurotoxic properties. A recent study in pregnant rats showed that DPAA crosses the placenta and reaches the fetal brain, raising concerns that it may disrupt the blood–brain barrier (BBB) since arsenic exposure induces BBB dysfunction. This study aimed to model gestational DPAA exposure, characterize its effects on birth outcomes, and evaluate its influence on neonatal nanoplastic brain accumulation. Pregnant mice received DPAA in drinking water from embryonic day 6 until birth, maternal body weight and pregnancy outcomes were monitored. Offspring received oral 50 nm NPs at postnatal day 0, and NP biodistribution was assessed using a workflow combining tissue optical clearing with light‑sheet fluorescence microscopy for whole‑brain mapping. DPAA exposure reduced live births, decreased neonatal body size, and caused retention of fetal membranes and umbilical cords. Imaging showed broadly comparable NP accumulation between DPAA‑exposed and control offspring brains, with region‑specific differences still under evaluation. These findings establish a gestational DPAA exposure model and provide an initial framework for determining whether prenatal toxicant‑induced BBB alterations may contribute to NP brain biodistribution during early development.