Abstract

BACKGROUND Atopic dermatitis (AD) is a common chronic inflammatory skin disorder. The association between early pregnancy exposure to organophosphate esters (OPEs) and the risk of infant AD, as well as the underlying mechanisms, remains unclear. METHODS Based on the Maternal Key Nutritional Factors and Offspring's Atopic Dermatitis (MKNFOAD) birth cohort, we assessed associations between first-trimester exposure to eight OPEs and offspring AD risk during the first year of life. A pregnant C57BL/6 mouse model exposed to OPEs was established; AD-like skin lesions were induced in the offspring using MC903. We investigated the effects of reactive oxygen species-mediated oxidative stress on skin lesions in pups and OPE-treated HaCaT cells. Transcriptomic analysis of OPE-treated HaCaT cells was performed to identify potential molecular pathways. RESULTS Early gestational exposure to Tris-2,3-dibromo propyl-phosphate (TDBPP) was associated with increased infant AD risk (adjusted odds ratio [OR] = 3.77, 95% confidence interval [CI]: 1.56-9.13, p < 0.01). Exploratory analyses suggested sex-specific associations between gestational OPE exposure and AD risk (TDBPP in boys: adjusted OR = 2.68, 95% CI: 0.99-7.27, p = 0.05; girls: adjusted OR = 10.88, 95% CI: 1.67-70.95, p = 0.01). Pups born to OPE-exposed dams exhibited greater ear thickness and more severe inflammatory infiltration than controls (p < 0.05). Transcriptomic analysis showed enrichment of tumor necrosis factor and MAPK signaling pathways in OPE-treated HaCaT cells. CONCLUSIONS This study provides evidence that early gestational exposure to TDBPP is associated with increased infant AD risk. Exploratory analyses suggest sex-specific effects. We also established an animal model and identified mechanistic pathways for future research.