Hum. Reprod. Advance Access originally published online on October 25, 2006
Human Reproduction 2007 22(3):702-707; doi:10.1093/humrep/del414
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Miglustat has no apparent effect on spermatogenesis in normal men
1 Department of Medicine 2 Department of Urology, University of Washington, Seattle, WA, USA 3 Schering AG, Berlin, Germany 4 Department of Ophthalmology, University of Washington, Seattle, WA and 5 Drug Metabolism, Berlex Biosciences, Richmond, CA, USA
6 To whom correspondence should be addressed at: Department of Medicine, University of Washington, Box 356429, 1959 NE Pacific Street, Seattle, WA 98195, USA. E-mail: jamory{at}u.washington.edu
BACKGROUND: In mice, administration of the glycosphingolipid biosynthesis inhibitor miglustat results in reversible infertilty, characterized by impaired sperm motility and markedly abnormal sperm morphology. This observation suggested that miglustat might have utility for fertility control in man. To ascertain the impact of miglustat on human spermatogenesis, we conducted a pilot study of miglustat administration in normal men. METHODS: After a 2-week baseline period, seven normal men were administered miglustat 100 mg, orally, twice daily for 6 weeks. During treatment, subjects had frequent seminal fluid analyses to assess the impact of treatment on sperm concentration, motility and morphology and the ability to undergo the acrosome reaction by in vitro assays. RESULTS: Five subjects completed all aspects of the study. In these subjects, there was no apparent effect of miglustat on sperm concentration, motility or sperm morphology after 6 weeks of therapy. In addition, no changes in acrosome structure or function were observed with treatment, despite therapeutic concentrations of miglustat in the serum and seminal plasma. All subjects experienced gastrointestinal upset, diarrhoea and mild weight loss during treatment. No other abnormalities in blood counts, serum chemistries, vision or overall health were observed. CONCLUSION: In contrast to the observations in mice, the oral administration of miglustat does not appear to affect human spermatogenesis. Further elucidation of the mechanism underlying the species specificity of miglustat may improve our understanding of the role of glycosphingolipids in spermatogenesis and result in alternative approaches to male fertility control.
Key words: miglustat/spermatogenesis/Gaucher disease/glycosphingolipid/male contraceptive
Submitted on August 28, 2006; resubmitted on September 19, 2006; accepted on September 26, 2006.
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