Abstract：
Bisphenol A (BPA) has been widely restricted, leading to a significant increase in the production of bisphenol AF (BPAF), one of the most common bisphenol analogs use as a substitute for BPA. However, there is limit evidence on the neurotoxicity of BPAF, especially the potential effects of maternal exposed to BPAF on offspring. A maternal BPAF exposure model was used to evaluate its effects on long-term neurobehaviors in offspring. We found that maternal BPAF exposure resulted in immune disorders, characterized by abnormal CD4+T cell subsets, and their offspring exhibited anxiety- and depression-like behaviors, as well as impairments in learning-memory, sociability and social novelty. Further, brain bulk RNA-sequencing (RNA-seq) and hippocampus single-nucleus RNA-sequencing (snRNA-seq) of offspring showed that differentially expressed genes (DEGs) were enriched in pathways related to synaptic and neurodevelopment. Synaptic ultra-structure of offspring was damaged after maternal BPAF exposure. In conclusion, maternal BPAF exposure induced behavior abnormality in adult offspring, together with synaptic and neurodevelopment defects, which might be related to maternal immune dysfunction. Our results provide a comprehensive insight into the neurotoxicity mechanism of maternal BPAF exposure during gestation. Given the increasing and ubiquitous exposure to BPAF, especially during sensitive periods of growth and development, the safety of BPAF requires urgent attention.
摘要：
双酚A(BPA)受到广泛的限制,导致双酚AF（BPAF）的产量显着增加，最常见的双酚类似物之一用作BPA的替代品。然而,关于BPAF的神经毒性的证据有限，特别是母亲暴露于BPAF对后代的潜在影响。使用母体BPAF暴露模型来评估其对后代长期神经行为的影响。我们发现母体BPAF暴露会导致免疫紊乱，以CD4+T细胞亚群异常为特征，他们的后代表现出焦虑和抑郁的行为，以及学习记忆障碍，社交性和社会新颖性。Further,后代的大脑整体RNA测序（RNA-seq）和海马单核RNA测序（snRNA-seq）显示，差异表达基因（DEG）富集了与突触和神经发育相关的途径。母体BPAF暴露后后代的突触超微结构受损。总之,母体BPAF暴露导致成年后代行为异常，连同突触和神经发育缺陷，这可能与母体免疫功能障碍有关。我们的结果为妊娠期母体BPAF暴露的神经毒性机制提供了全面的见解。鉴于BPAF的暴露越来越多，无处不在，特别是在生长发育的敏感时期，BPAF的安全性需要紧急关注。
