Abstract：
Bisphenol S (BPS) and Bisphenol F (BPF), the analogues of the legacy endocrine disrupting chemical, Bisphenol A (BPA) are ubiquitous in the environment and present in various consumer goods, and potentially neurotoxic. Here, we studied sex-specific responses of bisphenols on behavioural phenotypes, including their association with pro-inflammatory biomarkers and altered neurotransmitters levels, and the key gut microbial abundances. Neurobehavioural changes, using standard test battery, biochemical and molecular estimations for inflammatory cytokines, neurotransmitters, and oxido-nitrosative stress markers, gene expression analysis using qRT-PCR, H&E based histological investigations, gut permeability assays and Oxford Nanopore-based 16S-rRNA metagenomics sequencing for the gut microbial abundance estimations were performed. Bisphenol(s) exposure induces anxiety and depression-like behaviours, particularly in the male mice, with heightened pro-inflammatory cytokines levels and systemic endotoxemia, altered monoamine neurotransmitters levels/turnovers and hippocampal neuronal degeneration and inflammatory responses in the brain. They also increased gut permeability and altered microbial diversity, particularly in males. Present study provides evidence for sex-specific discrepancies in neurobehavioural phenotypes and gut microbiota, which necessitate a nuanced understanding of sex-dependent responses to bisphenols. The study contributes to ongoing discussions on the multifaceted implications of bisphenols exposure and underscores the need for tailored regulatory measures to mitigate potential health risks associated with them.
摘要：
双酚S(BPS)和双酚F(BPF),遗留的内分泌干扰化学物质的类似物，双酚A（BPA）普遍存在于环境中，存在于各种消费品中，和潜在的神经毒性。这里,我们研究了双酚对行为表型的性别特异性反应，包括它们与促炎生物标志物和神经递质水平改变的关联，和关键的肠道微生物丰度。神经行为改变,使用标准测试电池，炎性细胞因子的生化和分子评估，神经递质,和氧化亚硝基胁迫标志物，使用qRT-PCR进行基因表达分析，基于H&E的组织学调查，进行了肠道通透性测定和基于牛津纳米孔的16S-rRNA宏基因组学测序，以进行肠道微生物丰度估计。双酚暴露会引起焦虑和抑郁样行为，特别是在雄性老鼠身上，促炎细胞因子水平升高和全身性内毒素血症，改变单胺类神经递质水平/失误和海马神经元变性和大脑中的炎症反应。它们还增加了肠道通透性，改变了微生物多样性，尤其是男性。本研究为神经行为表型和肠道微生物群的性别差异提供了证据，这就需要对双酚的性别依赖性反应有细致的了解。该研究有助于正在进行的关于双酚暴露的多方面影响的讨论，并强调需要采取量身定制的监管措施来减轻与其相关的潜在健康风险。
