The use of urinary creatine as a marker of testicular dysfunction

The aim of these studies was to evaluate the use of urinary creatine as a marker of testicular dysfunction in rats and humans by a) comparing urinary creatine with other markers of testicular dysfunction after the administration of various testicular toxicants, b) identifying and assessing possible sources of interference, and c) investigating the route by which creatine enters the urine from the testes. In rats acutely dosed with 2-methoxyethanol (2-ME) or cadmium chloride (CdC12), the significant increase in urinary creatine and the creatine:creatinine ratio was more sensitive than testes weights or serum testosterone and lactate dehydrogenase-C4 (LDH- C4) at detecting testicular damage. Acute dosing with 1,3-dinitrobenzene (1,3-DNB) caused a discrete testicular lesion but no creatinuria, while ethyl methane sulphonate (EMS) caused significant creatinuria, but no detectable effect on the testes or the other markers. Semi-chronic daily administration of retinoic acid (RA) caused a testicular lesion, but no change in urinary creatine or serum testosterone and LDH-C4. Creatine was present in rat testis in concentrations second only to the muscle. Some creatinuria occurred after food restriction for 48 h, and after dosing with 2,3,5,6-tetramethyl p-phenylenediamine (TMPD), a muscle toxicant, but only when testicular damage was present. Urinary creatine excretion was not significantly higher in sham-operated than vasectomized rats following acute administration of 2-ME or CdC12, suggesting that most of the creatine enters urine via the blood rather than the vasa deferentia. Urinary creatine and the creatine:creatinine ratio were increased in human male adults exposed to lead, ethanol or a mixture of solvents. Thus urinary creatine, an easily measured, non-invasive marker is potentially more sensitive than other markers at detecting testicular damage in rats, although it may not detect all types of testicular dysfunction, and may have a role in detecting testicular dysfunction in humans