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.我们发现，暴露于250μg/kg/天双酚A（Bisphenol A，BPA）的大鼠（BPA250组）在出生后第90天（PND 90）出现动情周期异常转变；而25μg/kg/天BPA暴露组（BPA25组）及1年龄大鼠的BPA250组均出现动情期延长，提示BPA25与BPA250可能发挥类似高剂量炔雌醇（EE2-05）的作用，干扰正常动情周期节律。为解析其潜在分子机制，我们对1年龄样本开展RNA测序（RNA-sequencing），发现BPA25与BPA250两组具有相似的基因特征。通路分析显示，两组共有的710个独特基因与雌二醇相关，且经疾病预测分析证实，这些基因同时与女性恶性肿瘤存在关联。