Preconceptional Exposure to Rare Earth Elements in Couples and Spontaneous Abortion Risk: The Potential Role of Oxidative Stress

Abstract The effects and mechanisms of preconception couples’ coexposure to rare earth elements (REEs)─emerging reproductive toxicants─on spontaneous abortion (SA) remain unclear. This nested case–control study included 326 SA couples and 326 matched controls from a multicenter preconception cohort in Anhui Province (2019–2021). Eight REEs and eight oxidative stress biomarkers (OSBs) were measured in preconception urine. Conditional logistic regression found that urinary concentrations of lanthanum, cerium, praseodymium, neodymium, and samarium in females and males were associated with SA risk. Weighted quantile sum regression indicated that mixed REEs exposure in males was associated with SA in female partners (Odds ratio (OR) = 1.82, 95%CI: 1.40–2.36); mixed REEs exposure in females was associated with their SA risk (OR = 1.33, 95%CI: 1.04–1.69). Dual high exposure to lanthanum, cerium, praseodymium, neodymium, samarium, and dysprosium conferred a higher risk than dual low exposure (P < 0.05), and high REE exposure (Q4) in either partner was associated with increased SA risk in female partners (OR = 2.17–6.57). The OSB, 4-hydroxy-2-nonenal mercapturic acid (HNE-MA), mediated 19.4% of the praseodymium-SA association in females (P < 0.05). This study provides the first epidemiological evidence that preconception REE coexposure in couples was associated with increased SA risk, likely through oxidative stress; yet, with no established safety thresholds, further validation, including animal studies, is warranted.