The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on fertility and early embryonic development in rats.
Based on its ability to chelate copper, TTM is being studied as an antiangiogenic agent for cancer therapy. The purpose of this study was to evaluate the toxicity of TTM and the protection of copper supplementation on the reproductive capability of male and female CD rats. Doses of 0, 1, 4, and 12 mg/kg/day with copper supplementation (110 mg/kg of diet) were given by gavage. There were no effects on the estrous cycle or reproductive indices, or maternal toxicity in any female dose group. Male rats given 12 mg/kg/day showed significant decreases in body weight gains and food consumption, and anemia. Serum ceruloplasmin levels were dose-dependently decreased in all male dose groups. Reduced epididymal weights, sperm counts, and sperm motility, sperm morphologic abnormalities and histopathologic changes in testis and epididymis occurred only at 12 mg/kg/day. Dietary copper supplementation prevented the adverse sperm effects produced by 12 mg/kg/day of TTM.
Lyubimov
Alexander V
AV
Toxicology Research Laboratory, University of Illinois at Chicago, 1940W Taylor Street, Chicago, IL 60612, USA. lyubimov@uic.edu
Smith
Jeffry A
JA
Rousselle
Serge D
SD
Mercieca
Michael D
MD
Tomaszewski
Joseph E
JE
Smith
Adaline C
AC
Levine
Barry S
BS
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D002570:Ceruloplasmin / Q000032:analysis; D002614:Chelating Agents / Q000633:toxicity*; D003300:Copper / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D008297:Male; D008982:Molybdenum / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000473:pathology
D002614:Chelating Agents; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases