PMID- 19302082
OWN - NLM
STAT- MEDLINE
DCOM- 20090907
LR  - 20131121
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Linking)
VI  - 33
IP  - 6
DP  - 2009 Jun
TI  - Ethanol-mediated fetal dysmorphology and its relationship to the ontogeny of 
      maternal liver metallothionein.
PG  - 1051-8
LID - 10.1111/j.1530-0277.2009.00926.x [doi]
AB  - BACKGROUND: Fetal zinc (Zn) deficiency arising from ethanol-induction of the 
      Zn-binding protein metallothionein (MT) in the mother's liver has been proposed 
      as a mechanism of teratogenicity. Here, we determine the ontogeny of MT and Zn 
      homeostasis in rats and mice and then examine the effect of acute ethanol 
      exposure in early embryonic development on this relationship. The protective 
      effect of Zn against ethanol-mediated fetal dysmorphology is also examined. 
      METHODS: Study 1: Maternal liver MT and Zn homeostasis was determined in 
      Sprague-Dawley rats and C57BL/6J mice throughout gestation. Study 2: Rats were 
      administered ethanol (25% in saline, intraperitoneal 0.015 ml/g) or vehicle alone 
      on gestational day (GD) 9. Maternal liver MT and Zn, and plasma Zn was determined 
      over the ensuing 24 hours. Study 3: Pregnant rats were treated with ethanol and 
      Zn (s.c. 2.5 microg Zn/g) on GD9 and fetal dysmorphology was assessed on GD 19. 
      RESULTS: Study 1: Maternal liver MT began to rise around GD 9 peaking on GD 15 
      before falling to nonpregnant levels around term. The pregnancy-related increase 
      in MT was associated with a fall in plasma Zn which was significantly lower on GD 
      15 thereafter returning to nonpregnant levels by parturition. Study 2: Ethanol 
      administered to pregnant rats on GD 9 resulted in a 10-fold induction of MT in 
      the maternal liver and was associated with a 33% rise in liver Zn and a 30% fall 
      in plasma Zn, 16 hours after treatment. Study 3: Ethanol treatment on GD 9 
      resulted in a significant increase in craniofacial malformations which were 
      prevented by concurrent Zn treatment. CONCLUSIONS: The findings indicate that 
      maternal liver MT levels are lowest in early gestation (before GD 10) making this 
      a sensitive period where ethanol-induction of MT can affect fetal Zn homeostasis 
      and cause fetal dysmorphology. The study further provides evidence of a 
      protective role for Zn against ethanol-mediated teratogenicity.
FAU - Coyle, Peter
AU  - Coyle P
AD  - Hanson Institute, Institute of Medical and Veterinary Science, Frome Road, 
      Adelaide, SA 5000. peter.coyle@imvs.sa.gov.au
FAU - Martin, Sean A
AU  - Martin SA
FAU - Carey, Luke C
AU  - Carey LC
FAU - Summers, Brooke L
AU  - Summers BL
FAU - Rofe, Allan M
AU  - Rofe AM
LA  - eng
PT  - Journal Article
DEP - 20090319
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Central Nervous System Depressants)
RN  - 3K9958V90M (Ethanol)
RN  - 9038-94-2 (Metallothionein)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Animals
MH  - Central Nervous System Depressants/*toxicity
MH  - Craniofacial Abnormalities/*chemically induced/prevention & control
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Ethanol/*toxicity
MH  - Female
MH  - Fetal Development/*drug effects
MH  - Fetus/drug effects/metabolism
MH  - Homeostasis/drug effects
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Metallothionein/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - Pregnancy, Animal/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Zinc/metabolism/pharmacology/therapeutic use
EDAT- 2009/03/24 09:00
MHDA- 2009/09/08 06:00
CRDT- 2009/03/24 09:00
PHST- 2009/03/24 09:00 [entrez]
PHST- 2009/03/24 09:00 [pubmed]
PHST- 2009/09/08 06:00 [medline]
AID - ACER926 [pii]
AID - 10.1111/j.1530-0277.2009.00926.x [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2009 Jun;33(6):1051-8. doi: 
      10.1111/j.1530-0277.2009.00926.x. Epub 2009 Mar 19.