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The distribution of neonicotinoids and their metabolites in paired semen and urine samples and associations with male reproductive hormones
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DOI：10.3389/fendo.2026.1829662.png)
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Abstract
En 中文
BackgroundNeonicotinoids (NEOs) are widely used pesticides with potential endocrine-disrupting properties; yet their distribution in human reproductive matrices and associations with male reproductive hormones remain unclear.MethodsWe analyzed 146 paired semen and urine samples to characterize the distribution of 14 NEOs and their metabolites (m-NEOs) and to examine associations with male reproductive hormones. Concentrations were compared across matrices; and associations with follicle-stimulating hormone (FSH); luteinizing hormone (LH); testosterone (T); prolactin (PRL); estradiol (E2); and the T/LH ratio were evaluated using exposome-wide association (EWAS); deletion–substitution–addition (DSA); and mixture models.ResultsDetection frequencies ranged from 43.2% to 100% in urine and 19.9% to 99.3% in semen; with Desnitro-dinotefuran (DN) and Desmethyl-acetamiprid (DM-ACE) predominant in urine and DN and Acetamiprid (ACE) enriched in semen. Partitioning analysis revealed three distinct compound clusters: (1) DN; ACE; and Imidacloprid-urea (IMI-urea) enriched in semen; (2) Dinotefuran-urea (UF); Imidacloprid (IMI); Imidaclothiz (IMIT); and 5-Hydroxy-imidacloprid (5-OH-IMI); and (3) DM-ACE; Desnitro-imidacloprid (DN-IMI); Desnitro-imidacloprid-olefin (DN-IMI-olefin); and Clothianidin (CLO) predominantly excreted in urine. In EWAS and DSA; several nominal associations with hormones were observed. Nominal associations were observed between seminal CLO and FSH; DN and E2; and urinary UF and LH; Thiacloprid (THCP) exposure showed nominal positive associations with PRL and E2. However; none remained significant after correction for multiple testing. Mixture models indicated no overall significant associations. Sensitivity analyses supported the robustness of key compound–hormone associations.ConclusionNEOs and m-NEOs show distinct partitioning patterns between urine and semen; suggesting differential tissue distribution. Although several nominal associations with reproductive hormones were identified; none remained statistically significant after multiple-testing correction; indicating that these findings should be considered hypothesis-generating rather than conclusive. Further studies with larger populations and repeated measurements are needed to validate these associations and clarify the reproductive implications of NEO exposure in men.
Keywords:
urine
semen
neonicotinoid insecticides
human biomonitoring
reproductive hormone
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