睪丸間質液中重金屬濃度於無精症男性之初步研究
許程皓¹、李麗花²、蔡承翰^1,3、黃逸修^1,3、陳威任^1,3、黃志賢^1,3、黃奕燊^1,3

¹臺北榮民總醫院泌尿部; ²臺北榮民總醫院病理檢驗部

³國立陽明交通大學書田泌尿科學研究中心

Heavy metal concentrations in testicular interstitial fluid

in azoospermic men: A pilot study

Chen-Hao Hsu, M.D., M.T.M.¹, Li-Hua Li, Ph.D.², Cheng-Han Tsai, M.D.^1,3,
Eric Yi-Hsiu Huang, M.D., Ph.D.^1,3, Wei-Jen Chen, M.D.^1,3, William J. Huang, M.D., Ph.D.^1,3,
I-Shen Huang, M.D., Ph.D.^1,3

¹ Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan

² Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

³ Department of Urology, School of Medicine, College of Medicine and Shu-Tien Urological

Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan

Introduction:

Environmental pollution is a recognized factor influencing male reproductive health. Heavy metals, characterized by high atomic density and bioaccumulation potential, act as endocrine-disrupting chemicals and may impair spermatogenesis. Although their presence in semen has been associated with fertility status, limited data exist on heavy metal concentrations within the testis itself. This study investigated the composition of testicular interstitial fluid (TIF) in men with azoospermia and examined potential correlations with hormonal profiles and sperm retrieval outcomes.

Material & Methods:

Between January and December 2023, men with non-obstructive azoospermia (NOA) undergoing microdissection testicular sperm extraction (mTESE) were prospectively enrolled. Clinical assessment included medical history, physical examination, and hormonal testing for follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin, and estradiol. Testicular testosterone and concentrations of 12 elements (Ag, Cu, Co, Cd, Fe, Mg, Mn, Ni, Pb, Ru, Tl, Zn) were quantified in TIF using liquid chromatography–tandem mass spectrometry. Non-normally distributed data were compared using the Mann-Whitney U test, and correlations were analyzed by Spearman’s rank method.

Results:

Thirty-four men with NOA were analyzed, including 19 with and 15 without successful spermretrieval. No significant differences were found in TIF concentrations of Ag, Cu, Co, Cd, Fe, Mg, Mn, Ni, Pb, Ru, Tl, or Zn between the two groups. Co was undetectable in all patients, and Ag and Zn were measurable in only six. Median (interquartile range) concentrations of Cu, Cd, Fe, Mg, Mn, Ni, Pb, Ru, and Tl were 0.49 (0.43-0.64), 0.004 (0.001-0.005), 2.95 (2.00-4.37), 14.07 (12.93-16.14), 0.18 (0.10-0.27), 0.06 (0.03-0.09), 0.08 (0.07-0.09), 49.42 (39.52-64.23), and 0.018 (0.010-0.026) ng/mL, respectively. Among men with successful retrieval, intratesticular testosterone showed a significant inverse correlation with intratesticular Fe concentration (r = -0.54, p = 0.021).

Conclusions:

Heavy metals accumulate within the testicular microenvironment of men with NOA. Although their concentrations did not differ by sperm retrieval outcome, elevated intratesticular Fe was inversely correlated with intratesticular testosterone levels, suggesting potential spermatogenic toxicity. Further studies are warranted to elucidate the mechanistic effects of heavy metals on testosterone biosynthesis and spermatogenesis.