Toxicological evidence suggests that microcystin-LR (MC-LR) may impair male reproductive function, but epidemiological data remain limited. We conducted a cross-sectional study in Henan Province to investigate the effects of MC-LR exposure on semen quality and the potential mediating roles of aging biomarkers, including sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL), as well as reproductive hormones. Urinary MC-LR concentrations were measured using a newly developed ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Generalized linear models were used to evaluate associations, and mediation analysis was conducted to quantify indirect effects. Furthermore, the role of oxidative stress in MC-LR-induced alterations of mtDNAcn and TL was examined in vitro using GC-1 cells. MC-LR exposure was associated with adverse changes in semen quality, reproductive hormones, and aging biomarkers. Mediation analysis revealed that follicle-stimulating hormone, sperm mtDNAcn, and sperm TL mediated the effects of MC-LR on the decline in semen quality (mediation proportion 8 %-55 %). Moreover, certain doses of MC-LR increased ROS, mtDNAcn, and TL in GC-1 cells, which were partially reversed by the antioxidant N-Acetyl-L-cysteine. These findings provide new evidence linking environmental MC-LR exposure to impaired male reproductive health, possibly attributable to accelerated aging processes mediated by oxidative stress.
Keywords: Follicle stimulating hormone; Microcystin-LR; Mitochondrial DNA copy number; Semen quality; Telomere length.
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