LIMITED EFFECTS OF OZONE EXPOSURE DURING PREGNANCY ON PHYSICAL AND NEUROBEHAVIORAL DEVELOPMENT OF CD-1 MICE

LIMITED EFFECTS OF OZONE EXPOSURE DURING PREGNANCY ON PHYSICAL AND NEUROBEHAVIORAL DEVELOPMENT OF CD-1 MICE
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DOI:
10.1006/taap.1994.1251
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发表时间:
1994-12-01
影响因子:
3.8
通讯作者:
ALLEVA, E
ALLEVA, E
中科院分区:
医学3区
文献类型:
--
作者:
BIGNAMI, G;MUSI, B;ALLEVA, E

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只有少数研究尝试在实验室啮齿动物中评估产前接触臭氧 (O-3) 引起的母体毒性和后代行为变化。特别是,没有关于母体暴露后小鼠后代行为发育的数据,尽管出于经济原因和为了提高后续高级研究(例如治疗基因型相互作用)的有效性,在行为畸胎学研究中越来越多地使用该物种。在本研究中,雌性 CD-1 小鼠在怀孕期间(第 7-17 天)暴露于不同的 O-3 浓度(0、0.4、0.8 或 1.2 ppm);为了避免产后母体影响造成混淆,所有仔猪在出生后不久就被分配到在怀孕期间未经处理或处理的寄养母鼠。母鼠的食物和水摄入量以及体重增加均以浓度依赖性方式下降。在持续接触过程中形成对这些影响的耐受性;食物的这种耐受性比水的耐受性更快。一些生殖性能指标,如足月妊娠比例、产仔数、性别比、死产频率和新生儿死亡率,未能显示对照动物和 O-3 动物之间的差异。 1.2 ppm 的后代出生后体重增加略有但显着下降。除此之外,O-3 幼崽的体细胞发育与对照组没有区别,除了睁眼延迟之外。然而,这种效应未能表现出显着的浓度依赖性。在一系列评估中都获得了负面结果:(i) 从出生到第 18 天各种反射和反应的发展(“狐狸电池”); (ii) 产后第 3、7 和 11 天的超声波发射; (iii) 60-61 天时由单胺类兴奋剂(d-苯丙胺)引起的活动、习惯、对不熟悉物体的反应和过度活跃。目前的数据与先前对妊娠期暴露于 O-3(1 和 1.5 ppm)后由其亲生母亲抚养的大鼠进行的研究不同,该研究显示躯体和神经行为发育受到严重损害(R. Kavlock、E. Meyer 和 C. T. Grabowski,1980,Toxicol. Lett. 5, 3-9)。这种差异,无论是由于物种因素、产后母体影响,还是在接触开始后和适应或耐受之前发生最大 O-3 影响(例如,对食物和水摄入)的时间,可能为理解怀孕和发育中的生物体中的 O-3 影响提供重要线索。 (C) 1994 年学术出版社
Only a few studies have attempted to assess in laboratory rodents the maternal toxicity and behavioral changes in offspring caused by prenatal exposure to ozone (O-3). In particular, no data are available concerning the behavioral development of mouse offspring after maternal exposure, despite the fact that increasing use is made of this species in behavioral teratology studies for reasons both of economy and in order to increase the effectiveness of subsequent higher-tier studies (e.g., of treatment-genotype interactions). In the present work, female CD-1 mice were exposed during pregnancy (Days 7-17) to different O-3 concentrations (0, 0.4, 0.8, or 1.2 ppm); to avoid confounding by postnatal maternal effects, all litters were assigned shortly after birth to foster dams neither treated nor handled during pregnancy. The dams' food and water intake and body weight gain were depressed in a concentration-dependent fashion. Tolerance to these effects developed during continuing exposure; such tolerance was faster in the case of food than water intake. Several measures of reproductive performance, such as proportion of pregnancies carried to term, litter size, sex ratio, frequency of stillbirth, and neonatal mortality, failed to show differences between control and O-3 animals. Postnatal body weight gain was slightly but significantly depressed in the 1.2 ppm offspring. Otherwise, the somatic development of O-3 pups was indistinguishable from that of controls, save for a delay in eye opening; this effect, however, failed to show a significant concentration dependence. Negative results were obtained in a wide range of assessments concerning (i) the development of various reflexes and responses (''Fox battery'') from birth to Day 18; (ii) ultrasonic emissions on Postnatal Days 3, 7, and 11; and (iii) activity, habituation, response to an unfamiliar object, and hyperactivity produced by a monoaminergic stimulant (d-amphetamine) at 60-61 days. The present data differ from those of a previous study on rats raised by their biological mothers after gestational exposure to O-3 (1 and 1.5 ppm), which showed a substantial impairment in somatic and neurobehavioral development (R. Kavlock, E. Meyer, and C. T. Grabowski, 1980, Toxicol. Lett. 5, 3-9). This difference, be it due to species factors, to postnatal maternal effects, or to the time of occurrence of maximal O-3 effects (e.g., on food and water intake) after the onset of exposure and before adaptation or tolerance, may provide significant cues for the understanding of O-3 effects in pregnant and developing organisms. (C) 1994 Academic Press, Inc.