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首页> 外文期刊>Environmental research >Dibutyl phthalate exposure during gestation and lactation in C57BL/6 mice: Maternal behavior and neurodevelopment in pups
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Dibutyl phthalate exposure during gestation and lactation in C57BL/6 mice: Maternal behavior and neurodevelopment in pups

机译：C57BL / 6小鼠在妊娠和哺乳期间邻苯二甲酸二丁酯的暴露：幼仔的母亲行为和神经发育

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摘要

Objectives: Neurotoxic effects of phthalate during pregnancy on immature brain of the offspring or mature brains of the mothers remain unclear. We examined the effect of dibutyl phthalate (DBP) exposure during gestation and lactation on the maternal behavior of mother mice and neurodevelopment in pups. Methods: Pregnant mice were treated orally with DBP (0, 50 and 100 mg/kg/day, N = 20 per group) from gestational day 13 to postnatal day (PND) 15. Maternal behavior was measured using pup retrieval and nest shape test at postpartum day 4. For the pups, the neurodevelopment was measured using negative geotaxis, cliff avoidance at PND 7, swimming test and olfactory orientation at PND 14. RNA and protein expressions in the brain cortex of 50 mg/kg/day and control group (0 mg/kg/day) were analyzed using microarray and Western blot analysis. Nissl-stained sections at the coronal level of interaural 2.56 mm, bregma -1,23 mm, were used for counting of dark cortical neurons in mother and pup mice. Results: DBP treated mother mice (50 and 100 mg/kg/day) showed poor maternal behavior, poor nesting and retrieval behavior compared to the control group (0 mg/kg/day). In brain cortex, DBP-treated mothers showed decrease in protein expression of Nr4a3, Egrl, Arc, BDNF and phosphorylation of AKT and CREB, were also decreased in cortex of DBP-treated mothers. Pups exposed to DBP showed significantly decreased scores in negative geotaxis at PND 7 and swimming scores and olfactory orientation tests at PND 14. The cortex of the DBP exposed pups showed increase in expression of dopamine receptor D2 gene. Nissl staining showed that the dark neurons were increased in cortex of DBP treated mothers and DBP exposed pups. Suggesting that phthalate may delay pup development indirectly through inadequate mothering as well as direct phthalate exposure on the brain. Conclusion: DBP exposure during gestation and lactation cause impairment in maternal behaviors and down-regulation of neuronal plasticity and survival signals. Pups of mothers with exposed to DBP, showed delayed neurodevelopment and dark neurons increase in brain cortex, suggesting that phthalate may delay pup development indirectly through inadequate mothering as well as direct phthalate exposure on the brain.
机译：目的：怀孕期间邻苯二甲酸酯对后代未成熟大脑或母亲成熟大脑的神经毒性作用尚不清楚。我们检查了妊娠和哺乳期间邻苯二甲酸二丁酯（DBP）暴露对母鼠的母性行为和幼犬神经发育的影响。方法：从妊娠第13天到出生后第15天，口服DBP（0、50和100 mg / kg /天，每组N = 20）对妊娠小鼠进行口服治疗。在产后第4天。对于幼崽，使用负地轴，在PND 7避开悬崖，游泳测试和在PND 14进行嗅觉取向来测量神经发育。对照组50毫克/千克/天，大脑皮层中的RNA和蛋白质表达。 （0 mg / kg / day）使用芯片和Western blot分析。在耳间2.56 mm的冠状水平上的尼氏染色切片，前-为-1,23 mm，用于对母鼠和幼仔的深色皮质神经元进行计数。结果：与对照组（0 mg / kg /天）相比，DBP处理的母鼠（50和100 mg / kg /天）表现出较差的母性行为，较差的筑巢和恢复行为。在大脑皮层中，接受DBP处理的母亲表现出Nr4a3，Egrl，Arc，BDNF的蛋白质表达下降，并且AKT和CREB的磷酸化在接受DBP处理的母亲的皮质中也减少。暴露于DBP的幼犬在PND 7处的负地轴性得分显着降低，而在PND 14处游泳和嗅觉定向测试的分数显着降低。暴露于DBP的幼犬的皮质显示多巴胺受体D2基因的表达增加。 Nissl染色显示，在接受DBP治疗的母亲和暴露于DBP的幼崽的皮质中，黑暗神经元增加。这表明邻苯二甲酸盐可能通过母体缺乏以及直接暴露于大脑而间接延迟幼崽的发育。结论：孕期和哺乳期的DBP暴露会导致母亲行为受损以及神经元可塑性和生存信号的下调。暴露于DBP的母亲的幼崽显示出大脑皮层神经发育迟缓和黑暗神经元增加，这表明邻苯二甲酸酯可能通过母体缺乏以及直接暴露于大脑而间接延迟幼崽的发育。

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  • 来源
    《Environmental research》 |2020年第3期|109025.1-109025.10|共10页
  • 作者

    Seong Mi Lee; Songhee Jeon; Ha Jin Jeong; Bung-Nyun Kim; Yeni Kim;

  • 作者单位

    Department of Mental Health Research National Center for Mental Health Seoul Republic of Korea;

    bDepartment of Biomedical Sciences Center for Creative Biomedical Scientists at Chonnam National University Gwangju Republic of Korea;

    Division of Child & Adolescent Psychiatry Department of Psychiatry and Institute of Human Behavioral Medicine Seoul National University College of Medicine Seoul Republic of Korea;

    Department of Mental Health Research National Center for Mental Health Seoul Republic of Korea Department of Psychiatry Donggvk University International Hospital Dongguk University Medical School Goyang Republic of Korea;

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  • 正文语种 eng
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  • 关键词

    Dibutyl phthalate; Maternal behavior; Neurodevelopment; Neuronal survival; Plasticity;

    机译：邻苯二甲酸二丁酯;产妇行为;神经发育;神经元存活;可塑性;

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