Kaimal Amrita, Hooversmith Jessica M, Mansi Maryam H Al, Holmes Philip V, MohanKumar Puliyur S, MohanKumar Sheba M J
Biomedical and Translational Sciences Institute, Neuroscience Division, University of Georgia, Athens, GA 30602, USA.
Department of Biomedical Sciences, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
J Xenobiot. 2024 Aug 1;14(3):1036-1050. doi: 10.3390/jox14030058.
This study examines the sex-specific effects of gestational exposure (days 6-21) to endocrine-disrupting chemicals such as bisphenol A (BPA), diethylhexyl phthalate (DEHP), or their combination on brain monoamine levels that play an important role in regulating behavior. Pregnant Sprague-Dawley rats were orally administered saline, low doses (5 µg/kg BW/day) of BPA or DEHP, and their combination or a high dose (7.5 mg/kg BW/day) of DEHP alone or in combination with BPA during pregnancy. The offspring were subjected to a behavioral test and sacrificed in adulthood, and the brains were analyzed for neurotransmitter levels. In the paraventricular nucleus, there was a marked reduction in dopamine levels ( < 0.01) in male offspring from the BPA, DEHP, and B + D (HD) groups, which correlated well with their shock probe defensive burying times. Neurotransmitter changes in all brain regions examined were significant in female offspring, with DEHP (HD) females being affected the most, followed by the B + D groups. BPA and/or DEHP (LD) increased monoamine turnover in a region-specific manner in male offspring ( < 0.05). Overall, prenatal exposure to BPA, DEHP, or their combination alters monoamine levels in a brain region-specific, sex-specific, and dose-dependent manner, which could have implications for their behavioral and neuroendocrine effects.
本研究考察了孕期暴露(第6 - 21天)于双酚A(BPA)、邻苯二甲酸二(2 - 乙基己基)酯(DEHP)等内分泌干扰化学物或其组合对大脑单胺水平的性别特异性影响,这些单胺在调节行为中起重要作用。怀孕的斯普拉格 - 道利大鼠在孕期经口给予生理盐水、低剂量(5 µg/kg体重/天)的BPA或DEHP及其组合,或单独给予高剂量(7.5 mg/kg体重/天)的DEHP或与BPA联合给予。子代在成年后接受行为测试并被处死,然后分析其大脑中的神经递质水平。在室旁核中,BPA、DEHP和B + D(高剂量)组雄性子代的多巴胺水平显著降低(< 0.01),这与其电击探针防御性埋入时间密切相关。在所有检测的脑区中,雌性子代的神经递质变化均显著,其中DEHP(高剂量)雌性受影响最大,其次是B + D组。BPA和/或DEHP(低剂量)以区域特异性方式增加了雄性子代的单胺周转率(< 0.05)。总体而言,孕期暴露于BPA、DEHP或其组合会以脑区特异性、性别特异性和剂量依赖性方式改变单胺水平,这可能对其行为和神经内分泌效应产生影响。