Department of Psychology, University of Illinois, Champaign, Illinois, USA,
Division of Nutritional Sciences, University of Illinois, Urbana, Illinois, USA.
Dev Neurosci. 2019;41(1-2):1-16. doi: 10.1159/000494879. Epub 2018 Dec 21.
Both high-fat diets (HFD) and bisphenol A (BPA), an environmental endocrine disruptor, are prevalent in industrialized societies. Previous studies have detected separate effects of BPA and HFD; however, none have assessed possible interactive effects. Here, pregnant dams consumed 0, 40, or 400 µg BPA/kg/day and were fed either a control (CON; 15.8% kcal fat) or HFD (45% kcal fat) from gestational day 2 through parturition. The pups were individually dosed with BPA from postnatal days (P) 1-10, while the dams continued to consume one of the two diets. Maternal behavior increased with the HFD while the offspring's periadolescent social play decreased with BPA, but no interactive effects were observed. Neither HFD nor BPA exposure changed performance on a social recognition task, and only BPA had an effect on the elevated plus maze. BPA increased several cytokines in the medial prefrontal cortex (mPFC) of P10 males but not females. Expression of several genes related to hormone synthesis and receptors, inflammation, oxidative stress, and apoptosis in the mPFC on P10 and P90 were altered due to BPA and/or HFD exposure with rare interactive effects. BPA resulted in an increase in the gene expression of Esr1 in the mPFC of females on both P10 and P90. Epigenetic analysis on P90 did not show a change in methylation or in the levels of pre-mRNA or microRNA. Thus, perinatal BPA and HFD have separate effects but rarely interact.
高脂肪饮食（HFD）和双酚 A（BPA）都是在工业化社会中普遍存在的环境内分泌干扰物。先前的研究已经检测到 BPA 和 HFD 的单独作用；然而，没有研究评估它们可能存在的交互作用。在这里，怀孕的母鼠从受孕日第 2 天到分娩期间分别摄入 0、40 或 400μg/kg/d 的 BPA，并喂食对照（CON；15.8%卡路里脂肪）或 HFD（45%卡路里脂肪）。幼鼠从出生后第 1 天到第 10 天单独接受 BPA 给药，而母鼠继续食用两种饮食中的一种。HFD 增加了母鼠的母性行为，而 BPA 则降低了幼鼠青春期前的社交玩耍行为，但没有观察到交互作用。无论是 HFD 还是 BPA 暴露都没有改变社交识别任务的表现，只有 BPA 对高架十字迷宫有影响。BPA 增加了 P10 雄性幼鼠的内侧前额叶皮质（mPFC）中的几种细胞因子，但对雌性幼鼠没有影响。由于 BPA 和/或 HFD 暴露，mPFC 中与激素合成和受体、炎症、氧化应激和细胞凋亡相关的几个基因的表达在 P10 和 P90 时发生了改变，并且很少有交互作用。BPA 导致雌性幼鼠 mPFC 中的 Esr1 基因表达在 P10 和 P90 时都增加。P90 的表观遗传分析没有显示甲基化或前体 mRNA 或 microRNA 水平的变化。因此，围产期 BPA 和 HFD 有单独的作用，但很少相互作用。
