Consumer Product Chemical Mixtures and Oxylipin-Mediated Inflammation and Oxidative Stress during Early Pregnancy: Findings from a Large US Pregnancy Cohort

Consumer product chemicals pose an environmental risk
to public
health. Exposure during pregnancy to consumer product chemicals, particularly
phthalates and phenols, may increase the susceptibility to pregnancy
disorders by dysregulating inflammation and oxidative stress. However,
existing studies rely on downstream and nonmodifiable markers of these
processes. Oxylipins are oxidized lipids that act as key upstream
drivers of inflammation and oxidative stress. Importantly, oxylipins
are responsive to therapeutic interventions and thus potentially modifiable.
Using recent advances in lipidomics and statistical approaches to
address both individual chemical biomarkers and their mixtures, we
determined associations between early pregnancy biomarkers of consumer
product chemical exposure and oxylipins in a large prospective cohort.
Overall, our results revealed associations among oxylipins produced
across several biosynthetic pathways, suggesting a pattern indicative
of dysregulated inflammation and elevated levels of oxidative stress.
Phthalate metabolites were the primary drivers of associations, particularly
for metabolites of low molecular weight phthalates, often used in
personal care products. However, we found similar associations for
a biomarker of a phthalate replacement that is increasingly used in
consumer products. Our study provides observational evidence of specific
physiological pathways that may be dysregulated by exposure to consumer
product chemicals, including legacy phthalates and phthalate replacements.

日用消费品化学品对公众健康构成环境风险。孕期暴露于日用消费品化学品，尤其是邻苯二甲酸盐（phthalates）与酚类（phenols）物质，可能通过失调炎症与氧化应激反应，增加孕妇罹患妊娠相关疾病的易感性。然而，现有相关研究多依赖于这些生理过程的下游不可调控标志物。氧化脂类（oxylipins）是经过氧化修饰的脂质，可作为炎症与氧化应激反应的关键上游调控因子。值得注意的是，氧化脂类可响应治疗干预，因此具备潜在可调控性。本研究借助近年来脂质组学（lipidomics）与统计学方法的进展，同时考量单一化学生物标志物及其混合物的影响，在大型前瞻性队列（prospective cohort）中分析了孕早期日用消费品化学品暴露生物标志物与氧化脂类之间的关联。整体而言，本研究结果显示多条生物合成途径产生的氧化脂类之间存在关联，提示存在炎症失调与氧化应激水平升高的特征模式。邻苯二甲酸盐代谢物是该关联的主要驱动因素，尤其是常用于个人护理产品的低分子量邻苯二甲酸盐的代谢产物。不过，本研究也发现，一种日益广泛应用于日用消费品的邻苯二甲酸盐替代物的生物标志物，也呈现出类似的关联模式。本研究通过观察性分析，证实了日用消费品化学品（包括传统邻苯二甲酸盐与邻苯二甲酸盐替代物）暴露可能失调的特定生理通路。