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Placental Dysfunction in Suramin-Treated Rats: Impact of Maternal Diabetes and Effects of Antioxidative Treatment

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Abstract

Objective

The aim of the present study was to evaluate a rat model of placental dysfunction/ preeclampsia in pregnancies complicated by maternal diabetes. A second objective was to evaluate the effects of vitamin E treatment in this model.

Methods

Normal and streptozotocin-induced diabetic rats of two different strains (U and H) were given intraperitoneal (IP) injections of the angiogenesis inhibitor Suramin (Sigma Chemical Co, St Louis, MO) or saline in early pregnancy, and fed standard or vitamin E— enriched food. The outcome of pregnancy was evaluated on gestational day 20.

Results

In both rat strains Suramin caused fetal growth retardation, decreased placental blood flow, and increased placental concentration of the isoprostane 8-iso-PGF2α. In the U rats Suramin also caused increased fetal resorption rate, increased maternal blood pressure, decreased renal blood flow, and diminished maternal growth. Diabetes caused severe maternal and fetal growth retardation, increased resorption rate, and increased placental 8-iso-PGF2α concentration independent of Suramin administration. The maternal and fetal effects of Suramin and diabetes were more pronounced in the U strain than in the H strain. Vitamin E treatment improved the status of Suramin-injected diabetic rats: in U rats the blood pressure increase was normalized; and in both U and H rats the decreased placental blood flow was marginally enhanced, and the increase in placental 8-iso-PGF2α was partly normalized by vitamin E.

Conclusion

Suramin injections to pregnant rats cause a state of placental insufficiency, which in U rats resembles human preeclampsia. The induction of this condition is at least partly mediated by oxidative stress, and antagonized by antioxidative treatment. Maternal diabetes involves increased oxidative stress, and causes both maternal and fetal morbidity, which are only marginally affected by additional Suramin treatment.

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Authors and Affiliations

  1. Departments of Medical Cell Biology and Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

    Peppi Nash MD, Matts Olovsson MD, PhD & Ulf J. Eriksson MD, PhD

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  1. Peppi Nash MD
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  2. Matts Olovsson MD, PhD
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  3. Ulf J. Eriksson MD, PhD
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Corresponding author

Correspondence to Ulf J. Eriksson MD, PhD.

Additional information

Supported by the Ernfors Family Fund, Swedish Diabetes Association, Novo Nordisk Foundation, Swedish Research Council (Grants No. 12X-7475, 12X-109, 73X-08683-16A), General Maternity Hospital Foundation, Magnus Bergvall’s Foundation, and Henning and Gosta Ankarstrand’s Foundation.

The authors are grateful to Lisbeth Sagulin for practical help during the investigation, and to Dr Parri Wentzel and Dr Leif Jansson for valuable comments and substantial support.

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Nash, P., Olovsson, M. & Eriksson, U.J. Placental Dysfunction in Suramin-Treated Rats: Impact of Maternal Diabetes and Effects of Antioxidative Treatment. Reprod. Sci. 12, 174–184 (2005). https://doi.org/10.1016/j.jsgi.2004.12.002

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