Environmental metal exposure, seminal plasma metabolome and semen quality: Evidence from Chinese reproductive-aged men

Environmental metal exposure has been associated with decreasing semen quality, but the effects of multiple metal exposure on seminal plasma metabolome remain obscure. In this study, semen and repeated urine samples from 551 volunteers were collected in Wuhan City. Heavy metals and trace elements were measured using inductively coupled plasma mass spectrometer, and seminal plasma metabolomes were acquired using liquid chromatography coupled with high-resolution mass spectrometry. Weighted gene co-expression network analysis showed more than half of the seminal plasma metals were associated with specific metabolite modules, whereas only a few urine metals presented weak associations, indicating that seminal plasma may be an ideal biological sample for male reproductive biomarker discovery and exposure risk assessment. Seminal plasma zinc (Zn) and selenium (Se) concentrations were significantly associated with 22 metabolites (e.g., glycerophospholipids, acyl-carnitines and amino acid derivatives). Among these metabolites, acyl-carnitines were positively associated with semen quality and sperm concentration. Moreover, acyl-carnitines were associated with both Zn and Se exposure, indicating the potential role of carnitine pathway in their toxicity mechanism. Our findings suggest that seminal plasma metabolome connects Zn and Se exposure and sperm concentrations in Chinese men of reproductive age.