PMID- 26074427
OWN - NLM
STAT- MEDLINE
DCOM- 20151116
LR  - 20181202
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 287
IP  - 3
DP  - 2015 Sep 15
TI  - Embryonic catalase protects against ethanol embryopathies in acatalasemic mice 
      and transgenic human catalase-expressing mice in embryo culture.
PG  - 232-9
LID - S0041-008X(15)30015-6 [pii]
LID - 10.1016/j.taap.2015.06.007 [doi]
AB  - Reactive oxygen species (ROS) have been implicated in the mechanism of ethanol 
      (EtOH) teratogenicity, but the protective role of the embryonic antioxidative 
      enzyme catalase is unclear, as embryonic activity is only about 5% of maternal 
      levels. We addressed this question in a whole embryo culture model. C57BL/6 mouse 
      embryos expressing human catalase (hCat) or their wild-type (C57BL/6 WT) 
      controls, and C3Ga.Cg-Cat(b)/J catalase-deficient, acatalasemic (aCat) mouse 
      embryos or their wild-type C3HeB/FeJ (C3H WT) controls, were explanted on 
      gestational day (GD) 9 (plug=GD 1), exposed for 24h to 2 or 4mg/mL EtOH or 
      vehicle, and evaluated for functional and morphological changes. hCat and C57BL/6 
      WT vehicle-exposed embryos developed normally, while EtOH was embryopathic in 
      C57BL/6 WT embryos, evidenced by decreases in anterior neuropore closure, somites 
      developed, turning and head length, whereas hCat embryos were protected 
      (p<0.001). Maternal pretreatment of C57BL/6 WT dams with 50kU/kg PEG-catalase 
      (PEG-cat) 8h prior to embryo culture, which increases embryonic catalase 
      activity, blocked all EtOH embryopathies (p<0.001). Vehicle-exposed aCat mouse 
      embryos had lower yolk sac diameters compared to WT controls, suggesting that 
      endogenous ROS are embryopathic. EtOH was more embryopathic in aCat embryos than 
      WT controls, evidenced by reduced head length and somite development (p<0.01), 
      and trends for reduced anterior neuropore closure, turning and crown-rump length. 
      Maternal pretreatment of aCat dams with PEG-Cat blocked all EtOH embryopathies 
      (p<0.05). These data suggest that embryonic catalase is a determinant of risk for 
      EtOH embryopathies.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Miller-Pinsler, Lutfiya
AU  - Miller-Pinsler L
AD  - Department of Pharmacology and Toxicology, Faculty of Medicine, University of 
      Toronto, Toronto, Ontario, Canada.
FAU - Wells, Peter G
AU  - Wells PG
AD  - Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, 
      Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, Faculty of 
      Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: 
      pg.wells@utoronto.ca.
LA  - eng
PT  - Journal Article
DEP - 20150611
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (catalase-polyethylene glycol)
RN  - 3K9958V90M (Ethanol)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 1.11.1.6 (Catalase)
SB  - IM
MH  - Abnormalities, Drug-Induced/embryology/enzymology/genetics/*prevention & control
MH  - Acatalasia/embryology/*enzymology/genetics
MH  - Animals
MH  - Catalase/genetics/*metabolism/pharmacology
MH  - DNA Damage
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Embryo Culture Techniques
MH  - Embryo, Mammalian/*drug effects/enzymology/pathology
MH  - Ethanol/*toxicity
MH  - Gene Expression Regulation, Developmental
MH  - Gene Expression Regulation, Enzymologic
MH  - Gestational Age
MH  - Humans
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Oxidative Stress
MH  - Polyethylene Glycols/pharmacology
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - Antioxidative enzyme
OT  - Catalase
OT  - Embryopathies
OT  - Ethanol
OT  - Fetal alcohol spectrum disorder
OT  - Reactive oxygen species
OT  - Teratogenicity
EDAT- 2015/06/16 06:00
MHDA- 2015/11/17 06:00
CRDT- 2015/06/16 06:00
PHST- 2015/02/16 00:00 [received]
PHST- 2015/05/02 00:00 [revised]
PHST- 2015/06/10 00:00 [accepted]
PHST- 2015/06/16 06:00 [entrez]
PHST- 2015/06/16 06:00 [pubmed]
PHST- 2015/11/17 06:00 [medline]
AID - S0041-008X(15)30015-6 [pii]
AID - 10.1016/j.taap.2015.06.007 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2015 Sep 15;287(3):232-9. doi: 
      10.1016/j.taap.2015.06.007. Epub 2015 Jun 11.