Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Molecular Toxicology Interdepartmental Program, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Environ Int. 2021 Jan;146:106260. doi: 10.1016/j.envint.2020.106260. Epub 2020 Nov 19.
Bisphenol A (BPA) is an industrial plasticizer widely found in consumer products, and exposure to BPA during early development has been associated with the prevalence of various cardiometabolic diseases including obesity, metabolic syndrome, type 2 diabetes, and cardiovascular diseases. To elucidate the molecular perturbations underlying the connection of low-dose prenatal BPA exposure to cardiometabolic diseases, we conducted a multi-dimensional systems biology study assessing the liver transcriptome, gut microbial community, and diverse metabolic phenotypes in both male and female mouse offspring exposed to 5 μg/kg/day BPA during gestation. Prenatal exposure to low-dose BPA not only significantly affected liver genes involved in oxidative phosphorylation, PPAR signaling and fatty acid metabolism, but also affected the gut microbial composition in an age- and sex-dependent manner. Bacteria such as those belonging to the S24-7 and Lachnospiraceae families were correlated with offspring phenotypes, differentially expressed liver metabolic genes such as Acadl and Dgat1, and key drivers identified in our gene network modeling such as Malat1 and Apoa2. This multiomics study provides insight into the relationship between gut bacteria and host liver genes that could contribute to cardiometabolic disease risks upon low-dose BPA exposure.
双酚 A（BPA）是一种广泛存在于消费品中的工业增塑剂，早期发育过程中接触 BPA 与各种代谢心血管疾病的流行有关，包括肥胖、代谢综合征、2 型糖尿病和心血管疾病。为了阐明低剂量产前 BPA 暴露与代谢心血管疾病之间联系的分子扰动，我们进行了一项多维系统生物学研究，评估了雄性和雌性小鼠后代在妊娠期间暴露于 5μg/kg/天时的肝脏转录组、肠道微生物群落和多种代谢表型。低剂量 BPA 的产前暴露不仅显著影响了参与氧化磷酸化、PPAR 信号和脂肪酸代谢的肝脏基因，而且还以年龄和性别依赖的方式影响了肠道微生物组成。属于 S24-7 和 Lachnospiraceae 科的细菌与后代表型相关，与差异表达的肝脏代谢基因如 Acadl 和 Dgat1 相关，并且我们的基因网络建模中确定的关键驱动因素如 Malat1 和 Apoa2 相关。这项多组学研究深入了解了肠道细菌与宿主肝脏基因之间的关系，这可能导致低剂量 BPA 暴露时代谢心血管疾病风险增加。
