Adverse Male Reproductive Effects following Subchronic Exposure of Rats to Sodium Dichloroacetate

Dichloroacetate (DCA) activates the pyruvate dehydrogenase complexenhancing carbohydrate and lactate utilization in animals. Asa result it is used clinically in the treatment of acute lacticacidosis and has therapeutic potential in the treatment of stroke.Adverse effects of chronic DCA treatment include poly-neuropathyand testicular degeneration. Since DCA is a principal productof the aqueous chlorination of fulvic acids concern has arisenregarding the agent's impact on environmental health. We treatedmale Long-Evans rats with 0, 31.25, 62.5, or 125 mg DCA/kg/dayby oral gavage for 10 weeks. Compared to controls, preputialgland and epididymis weights were reduced at 31.25 mg/kg, bodyand liver weights at 62.5 mg/kg, and accessory organ weightsat 125 mg/kg. Epididymal sperm counts were reduced and spermmorphology was impacted at the 62.5 and 125 mg/kg doses levels.Histologic examination of the testis and epididymis revealedinhibited spermiation in testes at the 125 mg/kg dose level.Computer-assisted sperm motion analysis revealed reductionsin percentage motile sperm, curvilinear and straight-line velocity,linearity, and amplitude of lateral head displacement at boththe 62.5 and the 125 mg/kg dose levels. In the assessment offertility after an overnight mating, the number of viable implantson Day 14 of gestation was decreased only in the highest dosegroup. These studies demonstrate adverse effects of NaDCA treatmenton the rat male reproductive system, primarily on the accessoryorgans and sperm within them at lower doses (31.25 and 62.5mg/kg), and on the testis at the highest dOSe (125 mg/kg).