The effect of occupational lead toxicity on testosterone secretion and the L-arginine nitric oxide pathway

Abstract

Endocrine-disrupting chemicals (EDCs), including heavy metals such as lead (Pb), interfere with hormonal homeostasis, particularly in the hypothalamic-pituitary-gonadal (HPG) axis. Occupational lead exposure is linked to male reproductive dysfunction and cardiovascular risk via oxidative stress and endothelial impairment. This study investigated the effects of chronic lead exposure on testosterone levels and the L-arginine-nitric oxide (NO) pathway, a key regulator of endothelial function. This case-control study compared 120 male workers with occupational lead exposure (in battery manufacturing and foundries) to 120 unexposed controls. Blood lead levels (BLLs) were quantified via inductively coupled plasma mass spectrometry (ICP-MS), while testosterone (total/free) and methylated arginine metabolites; asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and citrulline were analyzed using LC-MS/MS. Statistical analyses included t-tests and Pearson correlations to assess associations. Lead-exposed workers had significantly higher BLLs (31.76 ± 13.31 vs 1.72 ± 0.87 μg/dL), lower total testosterone (388.23 ± 71.78 vs 477.36 ± 104.21 ng/dL), and reduced arginine/ADMA ratios (432.48 ± 191.27 vs 544.33 ± 187.19), indicating endothelial dysfunction. Strong inverse correlations were observed between exposure duration, classified as 6 months to 1 year, 1 to 5 years, and >5 years, to evaluate its association with BLL, testosterone levels, and arginine metabolism markers. This study demonstrated that chronic occupational lead exposure significantly disrupted testosterone secretion and impaired the L-arginine-NO pathway, highlighting its dual threat to reproductive and cardiovascular health. The robust inverse correlations between BLL, testosterone, and arginine/ADMA ratios underscore the endocrine-disrupting and endothelial-damaging effects of lead. These findings support the routine biomonitoring of BLL, testosterone, and methylated arginine metabolites in high-risk occupations to enable early intervention and mitigate long-term health risks.