Endocrine Abstracts

Pregnancy complicated by pre-existing or gestational diabetes is associated with increased risk of maternal and fetal mortality and morbidity. The most common complication, macrosomia, occurs during the third trimester of pregnancy as a result of abnormal placental growth and increased transfer of nutrients to the fetus. We have previously demonstrated using an explant model of human placenta, that statins have the potential to limit placental growth. In this study we tested the potential for using statins as a therapy for reducing placental and therefore birth weight using mice heterozygous for a signalling-deficient leptin receptor (db/+) as a model of gestational diabetes. Eight week old db/+ females were mated to wild type males and then treated with pravastatin (15 mg/kg/day, administered via drinking water) from days E12.5–E18.5 (n=6) or throughout pregnancy (n=6). Fetal and placental weights were measured at E18.5, the mean of each litter was calculated and compared to those from db/+ untreated pregnant dams (n=8). Statistical analysis was performed by Mann-Whitney U test. Treatment of db/+ pregnant dams with pravastatin from E12.5–E18.5 had no significant effect on placental weight but caused a significant 4% increase in fetal weight (untreated: 1067±9 mg, treated: 1114±10 mg, P=0.002), indicating a 6% increase in placental efficiency (fetal-to-placental weight ratio; P=0.01). Surprisingly, administration of pravastatin throughout pregnancy had the opposite effect; placental weights were increased by 7% (untreated: 82±1 mg, treated: 88±8 mg, P=0.004) but there was no effect on fetal weight which suggests a reduction in placental efficiency. Placental and fetal growth exhibited different responses depending on timing of administration. Treatment throughout pregnancy made the placenta less efficient but this did not translate into an effect on fetal growth. Neither treatment regimen caused a reduction in birth weight, thus pravastatin is not a suitable treatment for preventing fetal overgrowth.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: Diabetes UK.