Adverse male reproductive effects following subchronic exposure of rats to sodium dichloroacetate.
Dichloroacetate (DCA) activates the pyruvate dehydrogenase complex enhancing carbohydrate and lactate utilization in animals. As a result it is used clinically in the treatment of acute lactic acidosis and has therapeutic potential in the treatment of stroke. Adverse effects of chronic DCA treatment include polyneuropathy and testicular degeneration. Since DCA is a principal product of the aqueous chlorination of fulvic acids concern has arisen regarding the agent's impact on environmental health. We treated male Long-Evans rats with 0, 31.25, 62.5, or 125 mg DCA/kg/day by oral gavage for 10 weeks. Compared to controls, preputial gland and epididymis weights were reduced at 31.25 mg/kg, body and liver weights at 62.5 mg/kg, and accessory organ weights at 125 mg/kg. Epididymal sperm counts were reduced and sperm morphology was impacted at the 62.5 and 125 mg/kg doses levels. Histologic examination of the testis and epididymis revealed inhibited spermiation in testes at the 125 mg/kg dose level. Computer-assisted sperm motion analysis revealed reductions in percentage motile sperm, curvilinear and straight-line velocity, linearity, and amplitude of lateral head displacement at both the 62.5 and the 125 mg/kg dose levels. In the assessment of fertility after an overnight mating, the number of viable implants on Day 14 of gestation was decreased only in the highest dose group. These studies demonstrate adverse effects of NaDCA treatment on the rat male reproductive system, primarily on the accessory organs and sperm within them at lower doses (31.25 and 62.5 mg/kg), and on the testis at the highest dose (125 mg/kg).
Toth
G P
GP
Reproductive and Developmental Biochemistry Branch, U.S. Environmental Protection Agency, Cincinnati, Ohio 45268.
Kelty
K C
KC
George
E L
EL
Read
E J
EJ
Smith
M K
MK
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000033:anatomy & histology / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005837:Genitalia, Male / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D013076:Sperm Count / Q000187:drug effects; D013077:Sperm Head / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
D003999:Dichloroacetic Acid