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Ethylene Glycol Teratogenicity: A Role for Embryonic Acidosis?

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Title: Ethylene Glycol Teratogenicity: A Role for Embryonic Acidosis?
Authors: Ritchie, Helen E1 helen.ritchie@sydney.edu.au, Moore, Nigel P2, Webster, William S3
Source: Toxicological Sciences. Feb2018, Vol. 161 Issue 2, p421-430. 10p. 3 Charts, 4 Graphs.
Subjects: Ethylene glycol, Teratogenicity testing, Glycolic acid, Embryology, Heart beat
Abstract: 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 concentrationdependent 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. [ABSTRACT FROM AUTHOR]
Copyright of Toxicological Sciences is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Ethylene Glycol Teratogenicity: A Role for Embryonic Acidosis?
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  Data: <searchLink fieldCode="AR" term="%22Ritchie%2C+Helen+E%22">Ritchie, Helen E</searchLink><relatesTo>1</relatesTo><i> helen.ritchie@sydney.edu.au</i><br /><searchLink fieldCode="AR" term="%22Moore%2C+Nigel+P%22">Moore, Nigel P</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Webster%2C+William+S%22">Webster, William S</searchLink><relatesTo>3</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22Toxicological+Sciences%22">Toxicological Sciences</searchLink>. Feb2018, Vol. 161 Issue 2, p421-430. 10p. 3 Charts, 4 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Ethylene+glycol%22">Ethylene glycol</searchLink><br /><searchLink fieldCode="DE" term="%22Teratogenicity+testing%22">Teratogenicity testing</searchLink><br /><searchLink fieldCode="DE" term="%22Glycolic+acid%22">Glycolic acid</searchLink><br /><searchLink fieldCode="DE" term="%22Embryology%22">Embryology</searchLink><br /><searchLink fieldCode="DE" term="%22Heart+beat%22">Heart beat</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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 concentrationdependent 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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Toxicological Sciences is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1093/toxsci/kfx225
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      – Code: eng
        Text: English
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        PageCount: 10
        StartPage: 421
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      – SubjectFull: Ethylene glycol
        Type: general
      – SubjectFull: Teratogenicity testing
        Type: general
      – SubjectFull: Glycolic acid
        Type: general
      – SubjectFull: Embryology
        Type: general
      – SubjectFull: Heart beat
        Type: general
    Titles:
      – TitleFull: Ethylene Glycol Teratogenicity: A Role for Embryonic Acidosis?
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            NameFull: Moore, Nigel P
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              Text: Feb2018
              Type: published
              Y: 2018
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