Skip to main content

Advertisement

SpringerLink
Log in

Markers of Oxidative Stress in Placental Villi Exposed to Ethanol

  • Original Articles
  • Published:
The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

Ethanol exposure during pregnancy may result in fetal alcohol syndrome (FAS). The mechanism by which this occurs is unknown. Recent studies in several organ systems, including the placenta, suggest that oxidative stress is involved. In this study we investigated the presence and levels of three oxidative stress markers in placental villous tissue exposed to ethanol.

Methods

Villous tissues from normal placentas were perfused with Dulbeco’s modified Eagle’s medium (DMEM) with HEPES buffer, sodium bicarbonate, and glucose at pH 7.4. After stabilization, 100 mM ethanol was added to the pefusate. After 2 hours of pe fusion, the tissue was removed, fixed and stained for nitrotyrosine, 4-hydroxy-2-nonenal (4HNE) and 8-hydroxyguano sine (8-OHDG). Staining within the trophoblasts was quantified with densitometry.

Results

Nitrotyrosine and 4HNE immunostaining was seen in the trophoblasts. 4HNE was also seen in the stroma. In contrast, 8-OHDG was seen only in the stroma and endothelial cells in the fetal circulation. Ethanol exposure significantly increased nitrotyrosine levels in the trophoblasts beyond levels in the control tissue. Nitrotyrosine and 8-OHDG levels were also increased in stroma.

Conclusion

Within the placental villi, markers of oxidative stress are present in the trophoblasts and stroma after a short period of ethanol exposure. There is an increase in oxidative stress, primarily involving the nitric oxide pathway, in the trophoblasts as well as DNA damage in the stroma. Lipid peroxidation is not acutely changed in our 2-hour exposure window. (J Soc Gynecol Investig 2006; 13: 118—21) Copyright © 2006 by the Society for Gynecologic Investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Weiss M, Cronk CE, Mahkorn S, Glysch R, Zirbel S. The Wisconsin Fetal Alcohol Syndrome Screening Project. WMJ 2004;103:53–60.

    PubMed  Google Scholar 

  2. Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J 1996;10:709–20.

    Article  CAS  Google Scholar 

  3. Radi R, Cassina A, Hodara R, Quijano C, Castro L. Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 2002;33:1451–64.

    Article  CAS  Google Scholar 

  4. Juurlink BH, Paterson PG. Review of oxidative stress in brain and spinal cord injury: Suggestions for pharmacological and nutritional management strategies. Spinal Cord Med 1998;21:309–34.

    Article  CAS  Google Scholar 

  5. Hoek JB, Pastorino JG. Cellular signaling mechanisms in alcohol-induced liver damage. Semin Liver Dis 2004;24:257–72.

    Article  CAS  Google Scholar 

  6. Kay HH, Grindle KM, Magness RR. Ethanol exposure induces oxidative stress and impairs nitric oxide availability in the human placental villi: A possible mechanism of toxicity. Am J Obstet Gynecol 2000;182:682–8.

    Article  CAS  Google Scholar 

  7. Ischiropoulos H, Zhu L, Chen J, et al. Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 1992;298:431–7.

    Article  CAS  Google Scholar 

  8. Myatt L, Rosenfield RB, Eis AL, Brockman DE, Greer I, Lyall F. Nitrotyrosine residues in placenta. Evidence of peroxynitrite formation and action. Hypertension 1996;28:488–93.

    Article  CAS  Google Scholar 

  9. Takagi Y, Nikaido T, Toki T, et al. Levels of oxidative stress and redox-related molecules in the placenta in preeclampsia and fetal growth restriction. Virchows Arch 2004;444:49–55.

    Article  CAS  Google Scholar 

  10. Ahluwalia B, Smith D, Adeyiga O, Akbasak B, Rajguru S. Ethanol decreases progesterone synthesis in human placental cells: Mechanism of ethanol effect. Alcohol 1992;9:395–401.

    Article  CAS  Google Scholar 

  11. Karl PI, Fisher SE. Ethanol alters hormone production in cultured human placental trophoblasts. Alcohol Clin Exp Res 1993;17:816–21.

    Article  CAS  Google Scholar 

  12. Siler-Khodr TM, Yang Y, Grayson MH, Henderson GI, Lee M, Schenker S. Effect of ethanol on thromboxane and prostacyclin production in the human placenta. Alcohol 2000;21:169–80.

    Article  CAS  Google Scholar 

  13. Spong CY, Auth J, Vink J, Goodwin K, Abebe DT, Hill JM, Brenneman DE. Vasoactive intestinal peptide mRNA and immunoreactivity are decreased in fetal alcohol syndrome model. Regul Pept 2002;108:143–7.

    Article  CAS  Google Scholar 

  14. Marino MD, Aksenov MY, Kelly SJ. Vitamin E protects against alcohol-induced cell loss and oxidative stress in the neonatal rat hippocampus. Int J Dev Neurosci 2004;22:363–77.

    Article  CAS  Google Scholar 

  15. Siler-Marsiglio KI, Shaw G, Heaton MB. Pycnogenol and vitamin E inhibit ethanol-induced apoptosis in rat cerebellar granule cells. J Neurobiol 2004;59:261–71.

    Article  CAS  Google Scholar 

  16. Sureda A, Bade JM, Tauler P, et al. Hypoxia/reoxygenation and vitamin c intake influence no synthesis and antioxidant defenses of neutrophils. Free Radic Biol Med 2004;37:1744–55.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, 4301 W Markham, #518, Little Rock, Arkansas, 722205, USA

    Helen H. Kay MD, Stephen Tsoi PhD, Kreg Grindle BA & Ronald R. Magness PhD

  2. Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, Wisconsin, USA

    Helen H. Kay MD, Stephen Tsoi PhD, Kreg Grindle BA & Ronald R. Magness PhD

Authors
  1. Helen H. Kay MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen Tsoi PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kreg Grindle BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ronald R. Magness PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helen H. Kay MD.

Additional information

Supported by a grant from the National Institutes of Health (HD33843).

The authors thank Dr Zoran Bursac for his assistance with statistical analyses.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kay, H.H., Tsoi, S., Grindle, K. et al. Markers of Oxidative Stress in Placental Villi Exposed to Ethanol. Reprod. Sci. 13, 118–121 (2006). https://doi.org/10.1016/j.jsgi.2005.11.007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.jsgi.2005.11.007

Key words

Search

Navigation