Skip Navigation



Hum. Reprod. Advance Access published online on October 25, 2006
Human Reproduction, doi:10.1093/humrep/del414
This Article
Right arrow FREE Full Text (PDF ) Freely available
Right arrow All Versions of this Article:
22/3/702    most recent
del414v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Amory, J.K.
Right arrow Articles by Bremner, W.J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Amory, J.K.
Right arrow Articles by Bremner, W.J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 28, 2006
Revised September 19, 2006
Accepted September 26, 2006

Article

Miglustat has no apparent effect on spermatogenesis in normal men

J.K. Amory 1 *, C.H. Muller 2, S.T. Page 1, E. Leifke 3, E.R. Pagel 2, A. Bhandari 4, B. Subramanyam 5, W. Bone 3, A. Radlmaier 3, and W.J. Bremner 1

1 Department of Medicine, University of Washington, Seattle, WA, USA
2 Department of Urology, University of Washington, Seattle, WA, USA
3 Schering AG, Berlin, Germany
4 Department of Ophthalmology, University of Washington, Seattle, WA
5 Drug Metabolism, Berlex Biosciences, Richmond, CA, USA

* To whom correspondence should be addressed.
J.K. Amory, E-mail: jamory{at}u.washington.edu


  Abstract

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.

Keywords: miglustat/spermatogenesis/Gaucher disease/glycosphingolipid/male contraceptive.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 ReproductionHome page
P Sipila, J Jalkanen, I T Huhtaniemi, and M Poutanen
Novel epididymal proteins as targets for the development of post-testicular male contraception
Reproduction, March 1, 2009; 137(3): 379 - 389.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. T. Page, J. K. Amory, and W. J. Bremner
Advances in Male Contraception
Endocr. Rev., June 1, 2008; 29(4): 465 - 493.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.