氧化应激是将妊娠期接触邻苯二甲酸盐与婴儿期认知发展联系起来的潜在机制。

IF 2.6 3区医学 Q3 NEUROSCIENCES

Neurotoxicology and teratology Pub Date : 2024-10-01 DOI:10.1016/j.ntt.2024.107397

Kaegan E Ortlund , Susan L. Schantz , Andréa Aguiar , Francheska M. Merced-Nieves , Megan L. Woodbury , Dana E. Goin , Antonia M. Calafat , Ginger L. Milne , Stephanie M. Eick

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引用次数: 0

摘要

背景：妊娠期接触邻苯二甲酸盐（广泛用于消费品中的干扰内分泌的化学物质）与婴儿识别记忆力差有关。氧化应激可能是导致这种关联的途径之一。因此，我们研究了孕期接触邻苯二甲酸盐是否与氧化应激升高有关，以及氧化应激是否介导了接触邻苯二甲酸盐与识别记忆之间的关系：我们的分析包括伊利诺伊州儿童发展研究（IKIDS，N = 225，招募年份为 2013-2018 年）中的母子对子集。我们对孕期后三个月尿液样本中12种邻苯二甲酸酯代谢物的浓度进行了量化。在第二和第三孕期尿液中测量了四种氧化应激生物标志物（8-异前列腺素-PGF2α、2,3-二去甲-5,6-二氢-8-异PGF2α、2,3-二去甲-8-异PGF2α和前列腺素-F2α）。7个半月时对识别记忆进行评估，通过红外线眼动跟踪记录对熟悉和新奇刺激的注视时间。新奇偏好（与熟悉刺激配对时观察新奇刺激的时间比例）被认为是识别记忆的一个测量指标。线性混合效应模型用于估计邻苯二甲酸单乙酯（MEP）、邻苯二甲酸二（2-乙基己基）酯代谢物总和（ΣDEHP）、邻苯二甲酸二（异壬基）酯代谢物总和（ΣDINP）和抗雄激素邻苯二甲酸酯代谢物总和（ΣAA）与氧化应激生物标志物之间的关系。研究人员进行了中介分析，以评估氧化应激生物标志物是否介导了妊娠期邻苯二甲酸盐暴露对新奇偏好的影响：结果：产妇的平均分娩年龄为 31 岁，约 50% 的参与者拥有研究生学位。ΣAA、ΣDINP和ΣDEHP自然对数单位的增加与8-isoPGF2α、2,3-二去甲-5,6-二氢-8-isoPGF2α和2,3-二去甲-8-isoPGF2α的增加有显著的统计学关联。ΣAA与2,3-二去甲-5,6-二氢-8-异PGF2α的关联程度最大（β = 0.45，95 % 置信区间 = 0.14，0.76）。ΣAA、ΣDINP、ΣDEHP与新奇偏好之间的关系部分由2,3-二去甲-8-异PGF2α介导：结论：妊娠期接触某些邻苯二甲酸盐与氧化应激生物标志物呈正相关，凸显了这些化学物质可能损害早期认知发展的一个机制途径。

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Oxidative stress as a potential mechanism linking gestational phthalates exposure to cognitive development in infancy

Background

Gestational exposure to phthalates, endocrine disrupting chemicals widely used in consumer products, has been associated with poor recognition memory in infancy. Oxidative stress may represent one pathway linking this association. Hence, we examined whether exposure to phthalates was associated with elevated oxidative stress during pregnancy, and whether oxidative stress mediates the relationship between phthalate exposure and recognition memory.

Methods

Our analysis included a subset of mother-child pairs enrolled in the Illinois Kids Development Study (IKIDS, N = 225, recruitment years 2013–2018). Concentrations of 12 phthalate metabolites were quantified in 2nd trimester urine samples. Four oxidative stress biomarkers (8-isoprostane-PGF_2α, 2,3-dinor-5,6-dihydro-8-isoPGF_2α, 2,3-dinor-8-isoPGF_2α, and prostaglandin-F_2α) were measured in 2nd and 3rd trimester urine. Recognition memory was evaluated at 7.5 months, with looking times to familiar and novel stimuli recorded via infrared eye-tracking. Novelty preference (proportion of time looking at a novel stimulus when paired with a familiar one) was considered a measure of recognition memory. Linear mixed effect models were used to estimate associations between monoethyl phthalate (MEP), sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of di(isononyl) phthalate metabolites (ΣDINP), and sum of anti-androgenic phthalate metabolites (ΣAA) and oxidative stress biomarkers. Mediation analysis was performed to assess whether oxidative stress biomarkers mediated the effect of gestational phthalate exposure on novelty preference.

Results

The average maternal age at delivery was 31 years and approximately 50 % of participants had a graduate degree. A natural log unit increase in ΣAA, ΣDINP, and ΣDEHP was associated with a statistically significant increase in 8-isoPGF_2α, 2,3-dinor-5,6-dihydro-8-isoPGF_2α, and 2,3-dinor-8-isoPGF_2α. The association was greatest in magnitude for ΣAA and 2,3-dinor-5,6-dihydro-8-isoPGF_2α (β = 0.45, 95 % confidence interval = 0.14, 0.76). The relationship between ΣAA, ΣDINP, ΣDEHP, and novelty preference was partially mediated by 2,3-dinor-8-isoPGF_2α.

Conclusions

Gestational exposure to some phthalates is positively associated with oxidative stress biomarkers, highlighting one mechanistic pathway through which these chemicals may impair early cognitive development.

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来源期刊

Neurotoxicology and teratology 医学-毒理学

CiteScore

5.60

自引率

10.30%

发文量

审稿时长

58 days

期刊介绍： Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.