PMID- 29069465
OWN - NLM
STAT- MEDLINE
DCOM- 20190130
LR  - 20190130
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 161
IP  - 2
DP  - 2018 Feb 1
TI  - Editor's Highlight: Ethylene Glycol Teratogenicity: A Role for Embryonic 
      Acidosis?
PG  - 421-430
LID - 10.1093/toxsci/kfx225 [doi]
AB  - Ethylene glycol (EG) is a developmental toxicant in pregnant rats and mice. A 
      suggested mechanism for this toxicity is that the EG metabolite, glycolic acid 
      (GA), causes acidosis which may affect the embryonic heart rate (HR). This 
      inhibition would cause periods of embryonic bradycardia and arrhythmia resulting 
      in increased embryonic death and malformation in surviving embryos. This 
      hypothesis was investigated using gestational day (GD) 11 and 13 rat embryos in 
      vitro. Increasing concentrations of GA or lactic acid in the incubation medium 
      caused a decrease in external pH (pHe) and a concentration-dependent decrease in 
      embryonic HR. Increased concentrations of GA or lactic acid with pHe corrected to 
      normal levels did not affect HR. Severely decreased pHe, caused by reduced NaHCO3 
      in the incubation medium, had little effect on the HR of GD 13 embryos but 
      substantially reduced the HR of GD 11 embryos. These results suggest that 
      increased monocarboxylate concentration (glycolate or lactate) needs to be in 
      combination with increased H+ concentration (low pHe) to influence the embryonic 
      HR. These results implicate the monocarboxylate transporter reported to be 
      present in the early postnatal rat heart, the chick embryonic heart throughout 
      development, and the chorioallantoic placenta. The results showed some evidence 
      that the adverse effect of GA and reduced pHe on the embryonic HR increased with 
      duration of exposure and hence lends support to the suggested mechanism of 
      embryotoxicity for EG.
CI  - (c) The Author 2017. Published by Oxford University Press on behalf of the Society 
      of Toxicology. All rights reserved. For Permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Ritchie, Helen E
AU  - Ritchie HE
AD  - Discipline of Biomedical Science, Sydney Medical School, University of Sydney, 
      Lidcombe, NSW 2141, Australia.
FAU - Moore, Nigel P
AU  - Moore NP
AD  - Ubrs (Consulting) GmbH, Postfach, 4058 Basel, Switzerland.
FAU - Webster, William S
AU  - Webster WS
AD  - Department of Anatomy and Histology, Sydney Medical School, University of Sydney, 
      Sydney, NSW 2006, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Culture Media)
RN  - 0 (Glycolates)
RN  - 0WT12SX38S (glycolic acid)
RN  - FC72KVT52F (Ethylene Glycol)
SB  - IM
MH  - Acidosis/*chemically induced/embryology/physiopathology
MH  - Animals
MH  - Culture Media/chemistry
MH  - Embryonic Development/*drug effects
MH  - Ethylene Glycol/*toxicity
MH  - Gestational Age
MH  - Glycolates/*toxicity
MH  - Heart Rate/*drug effects
MH  - Hydrogen-Ion Concentration
MH  - In Vitro Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Teratogenesis/*drug effects
OTO - NOTNLM
OT  - acidosis
OT  - embryo
OT  - embryonic heart rate
OT  - in vitro
OT  - pH
EDAT- 2017/10/27 06:00
MHDA- 2019/01/31 06:00
CRDT- 2017/10/26 06:00
PHST- 2017/10/27 06:00 [pubmed]
PHST- 2019/01/31 06:00 [medline]
PHST- 2017/10/26 06:00 [entrez]
AID - 4562803 [pii]
AID - 10.1093/toxsci/kfx225 [doi]
PST - ppublish
SO  - Toxicol Sci. 2018 Feb 1;161(2):421-430. doi: 10.1093/toxsci/kfx225.