Kougias Daniel G, Cortes Laura R, Moody Laura, Rhoads Steven, Pan Yuan-Xiang, Juraska Janice M
Neuroscience Program, University of Illinois, Champaign, Illinois.
Department of Psychology, University of Illinois, Champaign, Illinois.
Endocrinology. 2018 Feb 1;159(2):1088-1105. doi: 10.1210/en.2017-03047.
Humans are ubiquitously exposed to many phthalates, a class of endocrine-disrupting chemicals commonly used in many consumer goods, and diet, especially fatty food, is presumed to be a major source of exposure. Here, we use a rat model of human prenatal exposure to investigate the potential interactive effects of an environmentally relevant mixture of phthalates and a maternal high-fat diet (HFD). From gestation through postnatal day (P)10, dams consumed the mixture of phthalates (0, 200, or 1000 μg/kg/d) and were fed a control diet or HFD. In males, perinatal exposure to the mixture of phthalates decreased prepubertal body weight and, in a dose-specific manner, periadolescent social play behavior. A dose-specific effect from phthalates with HFD was also seen in increased time alone in females during social play. HFD resulted in dams consuming more calories, having greater gestational weight gain, and licking and nursing their pups more, such that an early postnatal HFD generally increased pup body weight. There also was a tendency for increased oxidative stress markers at P10 within the medial prefrontal cortex of males exposed to the relatively high dose of phthalates and HFD. Effects on gene expression were inconsistent at P10 and P90 in both the medial prefrontal cortex and hypothalamus. Overall, this study demonstrates that phthalates and a maternal HFD only rarely interacted, except in oxidative stress markers in males. Additionally, perinatal exposure to an environmentally relevant mixture of phthalates can have a modest, but lasting, impact on social behaviors in both males and females.
人类普遍接触多种邻苯二甲酸盐，这是一类常用于许多消费品中的内分泌干扰化学物质，饮食，尤其是高脂肪食物，被认为是主要的接触源。在此，我们使用人类产前暴露的大鼠模型来研究邻苯二甲酸盐与母体高脂肪饮食（HFD）的环境相关混合物的潜在交互作用。从妊娠到出生后第10天，母鼠摄入邻苯二甲酸盐混合物（0、200或1000μg/kg/天），并喂食对照饮食或HFD。在雄性中，围产期暴露于邻苯二甲酸盐混合物会降低青春期前体重，并以剂量特异性方式减少青春期前后的社交玩耍行为。在雌性社交玩耍期间单独时间增加方面，也观察到邻苯二甲酸盐与HFD的剂量特异性效应。HFD导致母鼠消耗更多热量，孕期体重增加更多，舔舐和哺育幼崽更多，因此出生后早期HFD通常会增加幼崽体重。在暴露于相对高剂量邻苯二甲酸盐和HFD的雄性内侧前额叶皮质中，出生后第10天也有氧化应激标志物增加的趋势。在出生后第10天和第90天，内侧前额叶皮质和下丘脑的基因表达影响不一致。总体而言，本研究表明，邻苯二甲酸盐与母体HFD仅在少数情况下相互作用，除了雄性的氧化应激标志物。此外，围产期暴露于环境相关的邻苯二甲酸盐混合物会对雄性和雌性的社交行为产生适度但持久的影响。
