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围产期暴露于六溴环十二烷α-异构体对大鼠的短期影响:幼崽早期运动和感觉发育、自发运动活动及焦虑评估

Short-term effects of a perinatal exposure to the HBCDD α-isomer in rats: Assessment of early motor and sensory development, spontaneous locomotor activity and anxiety in pups.

作者信息

Maurice Nicolas, Olry Jean-Charles, Cariou Ronan, Dervilly-Pinel Gaud, Le Bizec Bruno, Travel Angélique, Jondreville Catherine, Schroeder Henri

机构信息

URAFPA, Université de Lorraine, INRA USC340, Vandoeuvre les Nancy, France.

LUNAM Université, Oniris, LABERCA, INRA USC1329, Nantes, France.

出版信息

Neurotoxicol Teratol. 2015 Nov-Dec;52(Pt B):170-80. doi: 10.1016/j.ntt.2015.08.005. Epub 2015 Sep 5.

Abstract

The present study investigated the developmental neurotoxicity of an early exposure to α-HBCDD through the ingestion of contaminated hen's egg in pregnant and lactating Wistar female rats. Hens were given α-HBCDD-contaminated feed (40 ng/g fresh matter) for 5 and 10 days, which produced eggs with HBCDD content of 33 and 102 ng/glipid weight, respectively. Female rats were administered daily p.o. with an appropriate volume of the whole egg from the day of fertilization (GD0) to the weaning day for pups (PND21). Fetuses and pups were thus exposed continuously to α-HBCDD via the dam over a whole 42-day period that included both gestation and lactation. The administered egg volume was calculated on the basis of daily egg consumption in humans (0.7 egg/person/day) and duration of gestation and lactation in both species, which led animals to be exposed to α-HBCDD at levels of 22 and 66 ng/kg/day, respectively. Neurobehavioral development of pups was investigated from PND3 to PND25 using various tasks including the righting reflex (PND4), the grasping reflex (PND5), the negative geotaxis (PND9), the forelimb grip strength test (PND10) and the locomotor coordination test (PND20). Pup ultrasonic vocalizations were also recorded daily from PND4 to PND14. After weaning, behaviors related to spontaneous locomotor activity and anxiety were examined in the open-field (PND25) and in an elevated-plus maze (PND26), respectively. The results showed a significant decrease in body weight of pups exposed to the lower HBCDD level from PND3 to PND28, whereas the weight of rat pups given 66 ng/kg/day of HBCDD was not different from controls. During the first 3 weeks of life, impairments in motor maturation of pups were observed in a dose-dependent manner depending on the test, whereas no significant differences were reported between male and female pups. At PND26, the anxiety level of female rats exposed to the lowest dose of HBCDD (22 ng/kg/day) was significantly reduced whereas it remained unchanged in males. No significant variations were measured in rats exposed to the higher level of HBCDD (66 ng/kg/day). These results suggest the potent developmental neurotoxicity of an early chronic exposure to the HBCDD α-isomer through the ingestion of hen's eggs contaminated with this pollutant and question the long-lasting consequences of this exposure on behavior abilities and brain functioning in adulthood.

摘要

本研究通过给怀孕和哺乳期的Wistar雌性大鼠喂食受污染的鸡蛋,调查了早期接触α-六溴环十二烷(α-HBCDD)的发育神经毒性。给母鸡喂食含α-HBCDD的饲料(40纳克/克鲜物质)5天和10天,所产鸡蛋的HBCDD含量分别为33和102纳克/克脂质重量。从受精日(GD0)到幼崽断奶日(PND21),每天给雌性大鼠经口灌胃适量的全蛋。因此,胎儿和幼崽在整个42天的时期内,包括妊娠期和哺乳期,通过母体持续接触α-HBCDD。灌胃的鸡蛋量是根据人类每日鸡蛋摄入量(0.7个鸡蛋/人/天)以及两种物种的妊娠期和哺乳期来计算的,这使得动物分别以22和66纳克/千克/天的剂量接触α-HBCDD。从PND3到PND25,使用各种任务对幼崽的神经行为发育进行了研究,包括翻正反射(PND4)、抓握反射(PND5)、负趋地性(PND9)、前肢握力测试(PND10)和运动协调测试(PND20)。从PND4到PND14,每天还记录幼崽的超声波发声。断奶后,分别在旷场实验(PND25)和高架十字迷宫实验(PND26)中检查与自发运动活动和焦虑相关的行为。结果显示,接触较低HBCDD剂量的幼崽从PND3到PND28体重显著下降,而给予66纳克/千克/天HBCDD的幼鼠体重与对照组无差异。在出生后的前三周,根据测试,幼崽的运动成熟受损呈剂量依赖性,而雄性和雌性幼崽之间未报告有显著差异。在PND26时,接触最低剂量HBCDD(22纳克/千克/天)的雌性大鼠的焦虑水平显著降低,而雄性大鼠的焦虑水平保持不变。接触较高水平HBCDD(66纳克/千克/天)的大鼠未测得显著变化。这些结果表明,通过摄入受该污染物污染的鸡蛋而早期长期接触HBCDDα异构体具有强大的发育神经毒性,并对这种接触对成年期行为能力和脑功能的长期影响提出了质疑。

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