PMID- 15576825
OWN - NLM
STAT- MEDLINE
DCOM- 20050830
LR  - 20220330
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 72
IP  - 4
DP  - 2005 Apr
TI  - 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.
PG  - 805-13
AB  - 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.
FAU - Suganuma, Ryota
AU  - Suganuma R
AD  - Institute for Biogenesis Research, University of Hawaii School of Medicine, 
      Honolulu, Hawaii 96822, USA.
FAU - Walden, Charlotte M
AU  - Walden CM
FAU - Butters, Terry D
AU  - Butters TD
FAU - Platt, Frances M
AU  - Platt FM
FAU - Dwek, Raymond A
AU  - Dwek RA
FAU - Yanagimachi, Ryuzo
AU  - Yanagimachi R
FAU - van der Spoel, Aarnoud C
AU  - van der Spoel AC
LA  - eng
GR  - 1 U01 HD45861/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041201
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Carbohydrates)
RN  - 0 (Contraceptive Agents, Male)
RN  - 0 (Disulfides)
RN  - 0 (Imines)
RN  - 0 (Protamines)
RN  - 0 (Sphingolipids)
RN  - 19130-96-2 (1-Deoxynojirimycin)
RN  - ADN3S497AZ (miglustat)
RN  - C4XNY919FW (migalastat)
SB  - IM
MH  - 1-Deoxynojirimycin/*analogs & derivatives/pharmacology
MH  - Alkylation
MH  - Animals
MH  - Carbohydrates
MH  - Contraceptive Agents, Male/*pharmacology
MH  - Disulfides/metabolism
MH  - Female
MH  - Fertility/drug effects/genetics
MH  - Fertilization in Vitro
MH  - Imines
MH  - Infertility, Male/chemically induced/*genetics/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Pregnancy
MH  - Pregnancy Outcome
MH  - Protamines/metabolism
MH  - Spermatozoa/*drug effects/*pathology/physiology
MH  - Sphingolipids/metabolism
EDAT- 2004/12/04 09:00
MHDA- 2005/09/01 09:00
CRDT- 2004/12/04 09:00
PHST- 2004/12/04 09:00 [pubmed]
PHST- 2005/09/01 09:00 [medline]
PHST- 2004/12/04 09:00 [entrez]
AID - biolreprod.104.036053 [pii]
AID - 10.1095/biolreprod.104.036053 [doi]
PST - ppublish
SO  - Biol Reprod. 2005 Apr;72(4):805-13. doi: 10.1095/biolreprod.104.036053. Epub 2004 
      Dec 1.