Low dose bisphenol A gene signature and endometrial cancer

We found rats exposed to 250ug/kg/day BPA (BPA250) showed abnormal transition in estrous cycle at postnatal (PND) 90 whereas 25ug/kg/day BPA (BPA25) and BPA250 in 1-year-old rats showed prolonged estrus phase, suggesting that BPA25 and BPA250 may act like high dose EE2 (EE2-05) in disrupting normal estrous cycling. To dissect the underlying molecular mechanism, we performed RNA-sequencing on 1-year-old samples and found that both BPA25 and BPA250 groups shared similar gene signature. Pathway analysis suggested that 710 unique genes from both groups were associated with estradiol and also linked to female cancer as suggested by disease prediction analysis. Five BPA exposed groups (2.5, 25,250,2500,25000ug/kg body weight); two EE2 exposed group (EE(0.5) and EE(0.05); One vehicle control group; n=4 per group;

本研究发现，暴露于250μg/kg/天双酚A（Bisphenol A，BPA）的大鼠在出生后第90天（PND 90）出现动情周期异常转变；而1岁龄大鼠暴露于25μg/kg/天BPA（BPA25）及BPA250组均表现出动情期延长，提示BPA25与BPA250可能类似高剂量雌二醇（EE2-05），可干扰正常动情周期节律。为解析其潜在分子机制，本研究对1岁龄大鼠样本开展RNA测序（RNA-sequencing），结果显示BPA25与BPA250组具有相似的基因表达特征。通路分析表明，两组共有的710个独特基因与雌二醇（estradiol）密切相关，且经疾病预测分析显示，这些基因同时与女性肿瘤存在关联。本实验共设置5个BPA暴露组（剂量分别为2.5、25、250、2500、25000μg/kg体重）、2个雌二醇暴露组（EE(0.5)与EE(0.05)）以及1个溶剂对照组，每组样本量n=4。