Doolittle Taylor, Duque-Wilckens Natalia
Department of Biological Sciences, College of Sciences, North Carolina State University, Raleigh, NC, USA.
Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
Adv Exp Med Biol. 2025;1477:281-309. doi: 10.1007/978-3-031-89525-8_11.
The development of the brain is a highly coordinated process that begins early in gestation and relies on intricate interactions between maternal and fetal immune systems. Disruptions to this delicate prenatal immune environment can significantly impact fetal brain development, increasing the risk of a spectrum of neurological and behavioral disorders, including autism spectrum disorder (ASD), schizophrenia, depression, and anxiety. While maternal exposure to viral and bacterial infections has been extensively studied as a driver of these disruptions, emerging research highlights the potential role of non-infectious exposures-such as drugs of abuse and environmental contaminants-in shaping neurodevelopmental outcomes. This issue has gained urgency with the rising prevalence of neurodevelopmental disorders; in the United States, for instance, ASD diagnoses have surged from 1 in 150 children in the early 2000s to 1 in 36 by 2020. Within this context, the increasing detection of cannabis, micro- and nanoplastics (MPs/NPs), and flame retardants in maternal and fetal tissues warrants close scrutiny. These substances, which are growing in prevalence due to changing societal norms, widespread environmental pollution, and industrial practices, may disrupt neurodevelopment through immune-mediated mechanisms. Cannabis use during pregnancy, for example, has increased significantly with legalization, while MPs/NPs and flame retardants are now frequently detected in maternal blood, placenta, and breast milk, raising concerns about their impacts on fetal health. In this chapter, we summarize human and preclinical evidence to explore how perinatal exposure to these substances may alter neurodevelopment by disrupting maternal and/or fetal immunity. We begin with an overview of central nervous system development and the critical role of immune interactions in ensuring a healthy pregnancy. We then review evidence linking perinatal exposure to cannabis, MPs/NPs, and flame retardants to neurodevelopmental outcomes, emphasizing immune-mediated pathways such as alterations in cytokine production, microglial activation, and adaptive immune cell function. Finally, we identify key gaps in the literature and propose future research directions to better understand the complex interplay between environmental exposures, immune dysregulation, and neurodevelopmental outcomes.
大脑发育是一个高度协调的过程，始于妊娠早期，依赖于母体和胎儿免疫系统之间复杂的相互作用。这种微妙的产前免疫环境受到干扰会显著影响胎儿大脑发育，增加一系列神经和行为障碍的风险，包括自闭症谱系障碍（ASD）、精神分裂症、抑郁症和焦虑症。虽然母体接触病毒和细菌感染作为这些干扰因素已得到广泛研究，但新兴研究突出了非感染性暴露（如滥用药物和环境污染物）在塑造神经发育结果方面的潜在作用。随着神经发育障碍患病率的上升，这个问题变得更加紧迫；例如，在美国，ASD的诊断率已从21世纪初的每150名儿童中有1例激增至2020年的每36名儿童中有1例。在此背景下，在母体和胎儿组织中越来越多地检测到大麻、微塑料和纳米塑料（MPs/NPs）以及阻燃剂，值得密切关注。由于社会规范的变化、广泛的环境污染和工业生产，这些物质的流行率不断上升，它们可能通过免疫介导机制扰乱神经发育。例如，随着大麻合法化，孕期大麻使用显著增加，而MPs/NPs和阻燃剂现在经常在母体血液、胎盘和母乳中被检测到，这引发了人们对它们对胎儿健康影响的担忧。在本章中，我们总结了人类和临床前证据，以探讨围产期接触这些物质如何通过扰乱母体和/或胎儿免疫来改变神经发育。我们首先概述中枢神经系统发育以及免疫相互作用在确保健康妊娠中的关键作用。然后，我们回顾将围产期接触大麻、MPs/NPs和阻燃剂与神经发育结果联系起来的证据，强调免疫介导途径，如细胞因子产生的改变、小胶质细胞激活和适应性免疫细胞功能。最后，我们确定文献中的关键空白，并提出未来的研究方向，以更好地理解环境暴露、免疫失调和神经发育结果之间的复杂相互作用。
