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...

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Bibliographic Details
Published in:Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2004-12, Vol.19 (2), p.223-233
Main Authors: Lyubimov, Alexander V., Smith, Jeffry A., Rousselle, Serge D., Mercieca, Michael D., Tomaszewski, Joseph E., Smith, Adaline C., Levine, Barry S.
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - antagonists & inhibitors
Animals
Ceruloplasmin
Ceruloplasmin - analysis
Chelating Agents - toxicity
Copper - administration & dosage
Copper depletion
Dose-Response Relationship, Drug
Early development
Embryonic Development - drug effects
Epididymis
Epididymis - drug effects
Epididymis - pathology
Estrous Cycle - drug effects
Female
Fertility - drug effects
Male
Molybdenum - toxicity
Organ Size - drug effects
Pregnancy
Rats
Rats, Inbred Strains
Reproduction
Sperm abnormalities
Spermatozoa - drug effects
Spermatozoa - pathology
Testis - drug effects
Testis - pathology
Tetrathiomolybdate
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Summary: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.
ISSN:0890-6238
1873-1708
DOI:10.1016/j.reprotox.2004.07.006