Document Detail

Alkylated imino sugars, reversible male infertility-inducing agents, do not affect the genetic integrity of male mouse germ cells during short-term treatment despite induction of sperm deformities.
MedLine Citation:
PMID:  15576825     Owner:  NLM     Status:  MEDLINE    
Reversible infertility can be induced in male mice by oral administration of the alkylated imino sugars N-butyldeoxynojirimycin (NB-DNJ) and N-butyldeoxygalactonojirimycin (NB-DGJ). Spermatozoa of these mice have grossly misshapen heads and reduced motility. Because NB-DNJ and related compounds may hold promise as nonhormonal male contraceptives, a comprehensive examination of their effects on male reproduction is necessary. To this end, we further examined reproductive properties of the dysmorphic spermatozoa that are produced after short-term imino sugar administration at the minimal dose that completely abolishes the ability of male C57BL/6 mice to produce offspring by natural mating. Here, we report that, in vitro, the abnormal spermatozoa from the NB-DNJ- and NB-DGJ-treated mice were unable to fertilize oocytes. In addition, we investigated whether the imino sugars damage the genetic integrity of spermatozoa. To test this, we microsurgically injected deformed spermatozoa from imino sugar-treated males into oocytes. The deformed spermatozoa from the testis were able to activate oocytes very efficiently, but those from the cauda epididymis often failed to do so. This problem was overcome when the sperm-injected oocytes were treated with a parthenogenetic agent, Sr(2+). Oocytes injected with the misshapen spermatozoa from NB-DNJ- and NB-DGJ-treated mice developed (with or without Sr(2+) treatment) into live offspring that grew normally and were normally fertile. This indicates that during short-term administration, alkylated imino sugars alter sperm morphology and physiology but do not diminish the genetic potential of spermatozoa.
Ryota Suganuma; Charlotte M Walden; Terry D Butters; Frances M Platt; Raymond A Dwek; Ryuzo Yanagimachi; Aarnoud C van der Spoel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-12-01
Journal Detail:
Title:  Biology of reproduction     Volume:  72     ISSN:  0006-3363     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-22     Completed Date:  2005-08-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  805-13     Citation Subset:  IM    
Institute for Biogenesis Research, University of Hawaii School of Medicine, Honolulu, Hawaii 96822, USA.
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MeSH Terms
1-Deoxynojirimycin / analogs & derivatives*,  pharmacology
Contraceptive Agents, Male / pharmacology*
Disulfides / metabolism
Fertility / drug effects,  genetics
Fertilization in Vitro
Infertility, Male / chemically induced,  genetics*,  pathology
Mice, Inbred C57BL
Mice, Inbred DBA
Pregnancy Outcome
Protamines / metabolism
Spermatozoa / drug effects*,  pathology*,  physiology
Sphingolipids / metabolism
Grant Support
Reg. No./Substance:
0/Carbohydrates; 0/Contraceptive Agents, Male; 0/Disulfides; 0/Imines; 0/N-butyldeoxygalactonojirimycin; 0/Protamines; 0/Sphingolipids; 0/miglustat; 19130-96-2/1-Deoxynojirimycin

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