NeuroBiologie de l'Olfaction, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
CALBINOTOX, Université de Lorraine, EA7488, Vandœuvre-lès-Nancy, France.
Part Fibre Toxicol. 2019 Jan 17;16(1):5. doi: 10.1186/s12989-018-0288-7.
Airborne pollution, especially from diesel exhaust (DE), is known to have a negative effect on the central nervous system in exposed human populations. However, the consequences of gestational exposure to DE on the fetal brain remain poorly explored, with various effects depending on the conditions of exposure, as well as little information on early developmental stages. We investigated the short-term effects of indirect DE exposure throughout gestation on the developing brain using a rabbit model. We analyzed fetal olfactory tissues at the end of gestation and tested behaviors relevant to pups' survival at birth. Pregnant dams were exposed by nose-only inhalation to either clean air or DE with a content of particles (DEP) adjusted to 1 mg/m by diluting engine exhaust, for 2 h/day, 5 days/week, from gestational day 3 (GD3) to day 27 (GD27). At GD28, fetal olfactory mucosa, olfactory bulbs and whole brains were collected for anatomical and neurochemical measurements. At postnatal day 2 (PND2), pups born from another group of exposed or control female were examined for their odor-guided behavior in response to the presentation of the rabbit mammary pheromone 2-methyl-3-butyn-2-ol (2MB2).
At GD28, nano-sized particles were observed in cilia and cytoplasm of the olfactory sensory neurons in the olfactory mucosa and in the cytoplasm of periglomerular cells in the olfactory bulbs of exposed fetuses. Moreover, cellular and axonal hypertrophies were observed throughout olfactory tissues. Concomitantly, fetal serotoninergic and dopaminergic systems were affected in the olfactory bulbs. Moreover, the neuromodulatory homeostasis was disturbed in a sex-dependent manner in olfactory tissues. At birth, the olfactory sensitivity to 2MB2 was reduced in exposed PND2 pups.
Gestational exposure to DE alters olfactory tissues and affects monoaminergic neurotransmission in fetuses' olfactory bulbs, resulting in an alteration of olfactory-based behaviors at birth. Considering the anatomical and functional continuum between the olfactory system and other brain structures, and due to the importance of monoamine neurotransmission in the plasticity of neural circuits, such alterations could participate to disturbances in higher integrative structures, with possible long-term neurobehavioral consequences.
空气中的污染物，特别是柴油机尾气（DE），已知会对暴露于其中的人群的中枢神经系统产生负面影响。然而，妊娠期接触 DE 对胎儿大脑的影响仍未得到充分探索，其后果取决于接触条件，而且关于早期发育阶段的信息也很少。我们使用兔模型研究了整个妊娠期间接接触 DE 对发育中大脑的短期影响。我们在妊娠末期分析了胎儿的嗅组织，并测试了与出生时幼崽生存相关的行为。妊娠母体通过鼻吸入仅暴露于清洁空气或 DE，DE 的颗粒含量（DEP）通过稀释发动机废气调整至 1mg/m，每天 2 小时，每周 5 天，从妊娠第 3 天（GD3）到第 27 天（GD27）。在 GD28 时，收集胎儿嗅黏膜、嗅球和整个大脑进行解剖和神经化学测量。在出生后第 2 天（PND2），检查来自另一组暴露或对照雌性的幼崽对兔乳腺信息素 2-甲基-3-丁炔-2-醇（2MB2）的嗅觉引导行为。
在 GD28 时，暴露胎儿的嗅黏膜嗅感觉神经元的纤毛和细胞质以及嗅球内的颗粒周围细胞的细胞质中观察到纳米级颗粒。此外，嗅组织中观察到细胞和轴突肥大。同时，嗅球中的胎儿 5-羟色胺能和多巴胺能系统受到影响。此外，嗅组织中的神经调节内稳态以性别依赖的方式受到干扰。出生时，暴露的 PND2 幼崽对 2MB2 的嗅觉敏感性降低。
妊娠期接触 DE 会改变胎儿嗅球的嗅组织并影响单胺能神经传递，导致出生时嗅觉行为发生改变。考虑到嗅觉系统与其他大脑结构之间的解剖和功能连续性，以及单胺能神经传递在神经回路可塑性中的重要性，这种改变可能会参与到高级整合结构的紊乱中，从而可能产生长期的神经行为后果。
