Ji Xiaotong, Jiang Peiyun, Li Yating, Su Lihong, Yue Huifeng, Sang Nan
Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China.
Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, Taiyuan, Shanxi 030001, P. R. China.
Environ Health (Wash). 2023 Sep 7;1(4):278-290. doi: 10.1021/envhealth.3c00085. eCollection 2023 Oct 20.
Breast cancer incidence has increased and become the world's most prevalent cancer, which is related to abnormal development of mammary glands and thought to be influenced by environment endocrine disruptors such as bisphenol A (BPA). However, whether its substitution, bisphenol B (BPB), has similar effects remains a concern. In the present study, a maternal exposure model of ICR mice combined time-series RNA-seq analysis was established to explore the underlying correlation among maternal BPB exposure (300 μg/kg body weight), mammary gland development, and long-term breast health in offspring. The results showed that BPB exposure disrupted hormonal homeostasis of the female offspring but did not affect the branch development of mammary glands in a time-dependent manner. However, at postnatal day 90 (PND90), BPB exposure resulted in duct dilatation, lobular hyperplasia, and inflammatory cell infiltration and increased the number of hormone receptor-expressing (HR) luminal cells in offspring. Further, the differentially expressed genes in time-series analysis of RNA-seq for mammary glands of the female offspring were enriched in the morphogenesis of branching structures, branching epithelium, and branching morphogenesis of epithelial tubes, which are always considered gland development. Interestingly, the results of RNA-seq also suggested that mRNA expression in the BPB group was elevated at PND90, and breast cancer related genes such as and were also altered. These findings suggested that maternal BPB exposure did not accelerate mammary gland development or lead to obvious morphological anomalies of offspring, but it induced pathological changes and altered cancer related gene expression in adult offspring breast.
乳腺癌发病率有所上升，已成为全球最常见的癌症，这与乳腺的异常发育有关，并且被认为受到环境内分泌干扰物如双酚A（BPA）的影响。然而，其替代物双酚B（BPB）是否具有类似作用仍是一个令人担忧的问题。在本研究中，建立了ICR小鼠母体暴露模型并结合时间序列RNA测序分析，以探究母体BPB暴露（300μg/kg体重）、乳腺发育与后代长期乳腺健康之间的潜在关联。结果表明，BPB暴露扰乱了雌性后代的激素稳态，但并未以时间依赖性方式影响乳腺的分支发育。然而，在出生后第90天（PND90），BPB暴露导致后代出现导管扩张、小叶增生和炎症细胞浸润，并增加了表达激素受体（HR）的管腔细胞数量。此外，对雌性后代乳腺进行RNA测序的时间序列分析中，差异表达基因富集于分支结构的形态发生、分支上皮以及上皮管的分支形态发生，这些通常被视为腺体发育过程。有趣的是，RNA测序结果还表明，BPB组在PND90时mRNA表达升高，并且与乳腺癌相关的基因如[此处原文缺失具体基因名称]也发生了改变。这些发现表明，母体BPB暴露并未加速后代乳腺发育或导致明显的形态异常，但它会诱导成年后代乳腺发生病理变化并改变癌症相关基因的表达。
