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

Matts Olovsson, MD, PhD

Departments of Medical Cell Biology and Women's and Children's Health, Uppsala University, Uppsala, Sweden

Ulf J. Eriksson, MD, PhD

Departments of Medical Cell Biology and Women's and Children's Health, Uppsala University, Uppsala, Sweden; Department of Medical Cell Biology, Uppsala University, Biomedical Center, P.O. Box 571, SE-751 23 Uppsala, Sweden; ulf.eriksson{at}medcellbiol.uu.se

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-PGF₂. 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-PGF₂, 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-PGF₂,, 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.

Key Words: Antioxidants • diabetes • placental dysfunction • preeclampsia • rat

Journal of the Society for Gynecologic Investigation, Vol. 12, No. 3, 174-184 (2005)
DOI: 10.1016/j.jsgi.2004.12.002


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