The dose-response relationship between seminal plasma metal mixtures and oligo-astheno-teratozoospermia: a hospital-based case-control study.

Oligo-astheno-teratozoospermia (OAT), a leading cause of male infertility, affects approximately 30 % of reproductive-aged men. While trace elements influence semen quality, prior investigations predominantly focused on single-element effects. Critical knowledge gaps persist regarding the combinatorial impacts of multi-element exposures on OAT pathogenesis. Our study enrolled 743 OAT cases and 179 controls. The seminal plasma element concentrations were quantified via inductively coupled plasma-mass spectrometry (ICP-MS). Analytical approaches mainly included restricted cubic splines (RCS) for dose-response modeling, and Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression to evaluate joint effects and identify primary contributors. The levels of seminal plasma calcium (Ca, p = 0.042), lithium (Li, p = 0.027), manganese (Mn, p = 0.009), cobalt (Co, p = 0.015), zinc (Zn, p = 0.021), and cadmium (Cd, p = 0.004) were significantly elevated in OAT patients. The dose-response relationships between OAT risks and seminal plasma metals were nonlinear for Li (pfor nonlinear = 0.042), and monotonic linear associations for Ca, Mn, Co, Zn, and Cd (all pfor nonlinear > 0.05). BKMR and WQS regression models demonstrated a positive overall mixture effect on OAT risk with Cd, Li, and Mn as primary drivers. This study provided novel evidence that seminal plasma trace elements dyshomeostasis, particularly involving Cd, Li, and Mn, was intricately linked to OAT risk through complex mechanisms.