Comprehensive Analysis of Mixed Reproductive Health Effects of Neonicotinoids: Association with Declining Sperm Concentration and Total Sperm Count in Men

Minimal studies focused on the association of mixed neonicotinoids (NEOs) exposure in seminal plasma with semen quality parameters, and further mixed effects on male reproductive health. In this study, we analyzed the concentrations of 6 parent neonicotinoids (p-NEOs) and 8 metabolite neonicotinoids (m-NEOs) using 155 male seminal plasma samples collected in Wuhan, China. Imidacloprid-olefin (IMI-olefin, 87.1%), acetamiprid-n-desmethyl (ACE-n-des, 74.2%), and 5-hydroxy-imidacloprid (IMI-5-OH, 80.0%) were dominant compounds, with median concentrations of 0.474, 0.294, and 0.277 ng/mL, respectively. Multivariate linear regression, and three mixture statistical models, including weighted quantile sum regression, quantile g-computation, and Bayesian kernel-machine regression models, were applied to explore the single and mixed effects of p-NEOs and m-NEOs exposure on semen quality. In the multivariate linear regression model, IMI-5-OH and thiacloprid-amide (TCP-Amide) were both significantly negatively associated with sperm concentration (β=-8.67, 95% CI = -16.26, -1.07, p  = 0.026; β=-7.85, 95% CI = -14.64, -1.05, p  = 0.024) and total sperm count (β=-17.32, 95% CI = -32.51, -2.13, p  = 0.026; β=-15.17, 95% CI = -28.77, -1.57, p  = 0.029). Similar results were observed in the mixture statistical models. These findings demonstrated a significantly detrimental impact of the NEOs mixture on both sperm concentration and total sperm count, with thiacloprid (TCP), IMI-olefin, IMI-5-OH, and TCP-Amide identified as the primary contributors. This study provided valuable insights into the potential mixed negative impacts of p-NEOs and m-NEOs on semen quality and offered a more comprehensive assessment of the reproductive health effects for p-NEOs and m-NEOs in the human body.