Journal Article

Repeated Analysis of Semen Parameters in Beagle Dogs during a 2-Year Study with the HMG-CoA Reductase Inhibitor, Atorvastatin

Lori A. Dostal, Paul Juneau and Charles E. Rothwell

in Toxicological Sciences

Volume 61, issue 1, pages 128-134
Published in print May 2001 | ISSN: 1096-6080
Published online May 2001 | e-ISSN: 1096-0929 | DOI:
Repeated Analysis of Semen Parameters in Beagle Dogs during a 2-Year Study with the HMG-CoA Reductase Inhibitor, Atorvastatin

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  • Medical Toxicology
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Sperm analyses are often incorporated into reproductive toxicity studies in rats. Due to the relative ease of collecting multiple samples throughout a study, semen analysis in non-rodents such as dogs offers the opportunity to assess potential development of functional effects of compounds on male reproduction over time. In the present study, semen parameters were evaluated in beagle dogs during and at termination of a chronic toxicity study with the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin. Male dogs received 0, 10, 40, or 120 mg/kg orally in gelatin capsules for up to 104 weeks (n = 10/group). After 52 weeks of dosing, 3 dogs/group were euthanized, and 2/group were withdrawn from treatment for a 12-week reversal period and euthanized at Week 64. The remaining 5/group continued treatment until Week 104. Semen was collected from all animals for 3 consecutive weeks prior to termination of the 52-week animals (Weeks 50, 51, 52) for analysis of sperm parameters, using manual methods of evaluation. Semen was collected from the remaining animals at Weeks 64, 78, 91, and 104, and was analyzed. At necropsy, testes, epididymides, and prostates were weighed and evaluated histologically, and epididymal sperm counts were determined. Serum cholesterol was decreased 25–60% at all doses during the study. There were no drug-related differences in semen volume and color, total sperm count, and sperm concentration, morphology, progressiveness, and percent motility during treatment with atorvastatin. There were also no effects on reproductive organ weights or histopathology, and no effects on epididymal sperm count. Thus, incorporation of semen analyses into this study allowed the evaluation of potential male reproductive effects in dogs at multiple time points during the study. Statistical power calculations demonstrated acceptable statistical power (> 80%) for semen sperm count, concentration, morphology, and motility with group sizes of 8–10 animals, and for semen sperm count and concentration or epididymal sperm count with group sizes of 3–5 animals, using the methodology described in this paper.

Keywords: sperm analysis; male beagle dogs; semen analysis; HMG-CoA reductase inhibitor; atorvastatin; sperm motility.

Journal Article.  5391 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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