Parental BPA exposure disrupts offspring transcriptomic profiles and impairs embryonic lineage specification during zygotic genome activation

IF 6.6 Q1 ENGINEERING, ENVIRONMENTAL
Yuequn Chen , Kusheng Wu , Wenlong Huang
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引用次数: 0

Abstract

Bisphenol A (BPA) is an endocrine-disrupting chemical known for its developmental toxicity. However, the impact of BPA on early embryonic development, particularly during zygotic genome activation (ZGA), remains underexplored. In this study, zebrafish embryos at 3.5 and 4.5 hours post-fertilization (hpf) were collected after 7-day parental exposure to 1.0 µM BPA for transcriptome sequencing. Transcriptomic data underwent differential gene expression functional enrichment and gene set enrichment analyses. Public single-cell transcriptome atlases of zebrafish embryos at different developmental stages (3.3, 4, and 4.8 hpf) were obtained to build signature matrices for digital cell type sorting of the bulk transcriptome using the CIBERSORTx algorithm. Results indicated that parental BPA exposure resulted in muted gene expression response, disturbed energy metabolism profile, and increased pro-inflammatory signatures during ZGA. Digital cell type deconvolution revealed altered cell composition, including deeper multilayer and enveloping layer cells and fewer margin cells. Furthermore, reductions in neural progenitor and heart primordium lineages, alongside expansions in primordial germ and mesendodermal lineages, potentially contribute to later-stage developmental abnormalities. This study elucidates the embryotoxic effects of BPA during the ZGA period, shedding light on the developmental perturbations from early-life exposure to this ubiquitous environmental contaminant.
父母双酚a暴露破坏后代转录组谱和损害胚胎谱系规范在合子基因组激活
双酚A (BPA)是一种内分泌干扰化学物质,以其发育毒性而闻名。然而,BPA对早期胚胎发育的影响,特别是在合子基因组激活(ZGA)期间,仍未得到充分研究。在本研究中,父母暴露于1.0 µM BPA 7天后,采集受精后3.5和4.5 小时(hpf)的斑马鱼胚胎进行转录组测序。转录组学数据进行了差异基因表达、功能富集和基因集富集分析。获取不同发育阶段(3.3、4和4.8 hpf)的斑马鱼胚胎的公开单细胞转录组图谱,利用CIBERSORTx算法构建标记矩阵,用于批量转录组的数字细胞类型分选。结果表明,父母双酚a暴露导致ZGA期间基因表达反应减弱,能量代谢谱紊乱,促炎特征增加。数字细胞类型反褶积显示细胞组成改变,包括多层和包络层细胞变深,边缘细胞变少。此外,神经祖细胞和心脏原基谱系的减少,以及原始生殖细胞和中胚层谱系的扩张,可能导致后期发育异常。本研究阐明了双酚a在ZGA时期的胚胎毒性作用,揭示了早期暴露于这种普遍存在的环境污染物对发育的干扰。
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来源期刊
Journal of hazardous materials letters
Journal of hazardous materials letters Pollution, Health, Toxicology and Mutagenesis, Environmental Chemistry, Waste Management and Disposal, Environmental Engineering
CiteScore
10.30
自引率
0.00%
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0
审稿时长
20 days
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