Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Center for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico.
Environ Res. 2023 Oct 15;235:116647. doi: 10.1016/j.envres.2023.116647. Epub 2023 Jul 12.
The biological pathways which link lead (Pb) and long-term outcomes are unclear, though rodent models and a few human studies suggest Pb may alter the body's stress response systems, which over time, can elicit dysregulated stress responses with cumulative impacts. This study examined associations between prenatal and early childhood Pb exposure and adolescent allostatic load, an index of an individual's body burden of stress in multiple biological systems, and further examined sex-based associations. Among 391 (51% male) participants in the ELEMENT birth cohort, we related trimester-specific maternal blood Pb, 1-month postpartum maternal tibia and patella Pb, and child blood Pb at 12-24 months to an allostatic load index in adolescence comprised of biomarkers of cardiovascular, metabolic, neuroendocrine, and immune function. The results were overall mixed, with prenatal exposure, particularly maternal bone Pb, being positively associated with allostatic load, and early childhood Pb showing mixed results for males and females. In adjusted Poisson regression models, 1 mcg/g increase in tibia Pb was associated with a 1% change in expected allostatic load (IRR = 1.01; 95%CI 0.99, 1.02). We found a significant Pb × sex interaction (IRR = 1.05; 95%CI 1.01, 1.10); where males saw an increasing percent change in allostatic load as 12 month Pb levels increased compared to females who saw a decreasing allostatic load. Further examination of allostatic load will facilitate the determination of potential mechanistic pathways between developmental toxicant exposures and later-in-life cardiometabolic outcomes.
将铅 (Pb) 与长期结果联系起来的生物学途径尚不清楚，尽管啮齿动物模型和一些人类研究表明，Pb 可能会改变人体的应激反应系统，随着时间的推移，这些系统会引发失调的应激反应，产生累积影响。本研究探讨了产前和幼儿期 Pb 暴露与青少年应激反应的累积负担之间的关联，这是一个个体在多个生物系统中应激负担的指标，并进一步探讨了基于性别的关联。在 ELEMENT 出生队列的 391 名参与者（51%为男性）中，我们将特定于三胞胎的母体血液 Pb、产后 1 个月母体胫骨和髌骨 Pb 以及 12-24 个月儿童血液 Pb 与青春期的应激反应累积负担指数相关联，该指数由心血管、代谢、神经内分泌和免疫功能的生物标志物组成。结果总体上是混合的，产前暴露，特别是母体骨骼 Pb，与应激反应累积负担呈正相关，而幼儿期 Pb 对男性和女性的影响则各不相同。在调整后的泊松回归模型中，胫骨 Pb 增加 1 mcg/g 与应激反应累积负担的预期变化 1%相关（IRR=1.01；95%CI 0.99，1.02）。我们发现 Pb 与性别之间存在显著的交互作用（IRR=1.05；95%CI 1.01，1.10）；与女性相比，男性随着 12 个月 Pb 水平的升高，应激反应累积负担的百分比变化增加，而女性的应激反应累积负担则减少。进一步研究应激反应累积负担将有助于确定发育毒物暴露与生命后期心血管代谢结局之间的潜在机制途径。
