Early-life bisphenol AP exposure impacted neurobehaviors in adulthood through microglial activation in mice.

Bisphenol AP (BPAP), a structural analog of bisphenol A (BPA), has been widely detected in environment and biota. BPAP was reported to interfere with hormone and metabolism, while limited data were available about its effects on neurobehavior, especially exposure to it during early-life time. A mouse model of early-life BPAP exposure was established to evaluate the long-term neurobehaviors in offspring. Collectively, early-life BPAP exposure caused anxiety-like behaviors and impaired learning and memory in adult offspring. Through brain bulk RNA-sequencing (RNA-seq), we found differential expressed genes were enriched in pathways related to behaviors and neurodevelopment, which were consistent with the observed phenotype. Besides, single-nucleus RNA-sequencing (snRNA-seq) showed BPAP exposure altered the transcriptome of microglia in hippocampus. Mechanistically, BPAP exposure induced inflammations in hippocampus through upregulating Iba-1 and activating the microglia. In addition, we observed that BPAP exposure could activate peripheral immunity and promote proportion of macrophages and activation of dendritic cells in the offspring. In conclusion, early-life exposure to BPAP impaired neurobehaviors in adult offspring accompanied with excessive activation of hippocampal microglia. Our findings provide new clues to the underlying mechanisms of BPAP's neurotoxic effects and therefore more cautions should be taken about BPAP.