Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing Medical University, Nanjing, China; School of Public Health, Southwest Medical University, Luzhou, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Microbiology and Infection, School of Public Health, Nanjing Medical University, Nanjing, China.
Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Microbiology and Infection, School of Public Health, Nanjing Medical University, Nanjing, China.
Chemosphere. 2023 Mar;317:137935. doi: 10.1016/j.chemosphere.2023.137935. Epub 2023 Jan 22.
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.
双酚 AP（BPAP）是双酚 A（BPA）的结构类似物，已在环境和生物群中广泛检出。有报道称 BPAP 会干扰激素和新陈代谢，而关于其对神经行为的影响，特别是在生命早期暴露的相关数据有限。本研究建立了生命早期 BPAP 暴露的小鼠模型，以评估后代的长期神经行为。总的来说，生命早期 BPAP 暴露导致成年后代出现焦虑样行为和学习记忆受损。通过大脑 bulk RNA-seq（RNA-seq），我们发现差异表达基因富集在与行为和神经发育相关的途径中，与观察到的表型一致。此外，单细胞 RNA-seq（snRNA-seq）显示 BPAP 暴露改变了海马体中小胶质细胞的转录组。从机制上讲，BPAP 暴露通过上调 Iba-1 并激活小胶质细胞在海马体中引起炎症。此外，我们观察到 BPAP 暴露可激活外周免疫，增加后代中巨噬细胞和树突状细胞的比例。总之，生命早期暴露于 BPAP 会损害成年后代的神经行为，同时伴有海马体中小胶质细胞过度激活。我们的研究结果为 BPAP 的神经毒性作用的潜在机制提供了新的线索，因此应更加谨慎地对待 BPAP。
