Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Sodium thiosulfate in the pregnant Dahl salt-sensitive rat: a solution to preeclampsia and fetal growth restriction? (#16)

Fieke Terstappen 1 2 , Sinéad M. Clarke 2 , Jaap A. Joles 3 , Courtney A. Ross 4 , Michael R. Garrett 4 , Harry van Goor 5 , Jennifer M. Sasser 4 , A. Titia Lely 2
  1. Department for Developmental Origins of Disease, Wilhelmina Children's Hospital and UMC Utrecht Brain Center, Utrecht, The Netherlands
  2. Department of Obstetrics, Wilhelmina Children's Hospital Birth Center, University Medical Center Utrecht, Utrecht, The Netherlands
  3. Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  4. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA
  5. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Background: The gasotransmitter hydrogen sulfide (H2S) has pro-angiogenic, anti-oxidant and anti-inflammatory properties necessary for normal vascular adaptations during pregnancy. Subnormal production of H2S has been linked to preeclampsia. A growing body of evidence supports the therapeutic potential of H2S in preeclampsia. Thus, we hypothesized that sodium thiosulfate (STS) – a H2S donor – would reduce maternal hypertension and proteinuria and diminish fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preeclampsia.

Methods: Pregnant Dahl S rats (n=30) were divided into three groups. Two groups received STS via drinking water at a dose of 2g per kg body weight per day (n=9) or 3g per kg body weight per day (n=8) from gestational day (GD) 10-20; the third group (n=13) received no treatment. Uterine artery resistance index was measured on GD18. On GD19, 24-hour urine was collected to determine maternal proteinuria. On GD20, intra-arterial blood pressure and fetal outcome (fetal and placental weight, litter size and fetal demise) were evaluated. Renal injury was histologically scored.

Results: STS dosed at 2g per kg body weight per day had no effect on preeclamptic symptoms or fetal outcome. At 3g per kg body weight per day, STS reduced maternal hypertension by 14 mmHg (121.8±3.0 vs 136.3±2.9; p<0.05), but increased proteinuria (89±15 vs 56±5 mg/24h; p<0.05) and relative kidney weight (0.86±0.04 vs 0.73±0.02%; p<0.05). Fetal:placental weight-ratio was reduced (3.83±0.07 vs 4.31±0.08; p<0.01) with no effect on fetal or placental weight or litter size. No differences in uterine artery flow or renal damage were noted across treatment groups.

Conclusion: While these data suggest a promising antihypertensive effect that could imply prolongation of preeclamptic pregnancies, the worrisome effect on fetal:placental weight-ratio, proteinuria and kidney weight implies that clinical implementation of STS is contra-indicated until safety for mother and child can be warranted.