title: Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates.
abstract: Resveratrol has been proposed as a potential therapeutic to improve metabolic health during pregnancy, yet little is known about the fetal effects of this maternal dietary supplement. We hypothesized that when administered to pregnant nonhuman primates (NHPs), resveratrol would increase uterine blood flow and mitigate the harmful consequences of maternal Western-style diet (WSD) consumption. NHPs were fed a WSD (36% fat) supplemented with 0.37% resveratrol throughout pregnancy. Outcomes were compared with cohorts fed WSD alone and control chow (14% fat) to distinguish between WSD and resveratrol-specific effects in these animals. In the early third trimester, uterine blood flow was measured by Doppler ultrasound before fetal delivery and tissue collection. Resveratrol resulted in 30% maternal weight loss and improved glucose tolerance, increased uterine artery volume blood flow, and decreased placental inflammation and liver triglyceride deposition. In addition, fetal pancreatic mass was enlarged by 42%, with a 12-fold increase in proliferation by Ki67 immunohistochemistry. These results demonstrate that resveratrol use during pregnancy yields improvements in maternal and placental phenotype with beneficial effects in the fetal liver but an unexplained and concerning alteration in fetal pancreatic development, which strongly cautions against the use of resveratrol by pregnant women.
authors.affiliation: Division of Diabetes, Obesity, and Metabolism and.
authors.forename: Victoria H J
authors.initials: VH
authors.lastname: Roberts
authors.affiliation: Division of Diabetes, Obesity, and Metabolism and.
authors.forename: Lynley D
authors.initials: LD
authors.lastname: Pound
authors.affiliation: Department of Pediatrics and.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Thorn
authors.affiliation: Department of Medical and Molecular Genetics.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: Gillingham
authors.affiliation: Knight Cardiovascular Institute, and.
authors.forename: Kent L
authors.initials: KL
authors.lastname: Thornburg
authors.affiliation: Department of Pediatrics and Department of Reproductive Sciences, University of Colorado-Denver, Aurora, Colorado, USA;
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Friedman
authors.affiliation: Division of Diabetes, Obesity, and Metabolism and Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Frias
authors.affiliation: Division of Diabetes, Obesity, and Metabolism and Division of Reproductive and Developmental Science, Oregon National Primate Research Center, Beaverton, Oregon USA; grovek@ohsu.edu.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
mesh_terms: D000818:Animals; D000075202:Contraindications; D004032:Diet / Q000009:adverse effects; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005333:Fetus; D008099:Liver / Q000187:drug effects / Q000196:embryology; D008251:Macaca; D010179:Pancreas / Q000187:drug effects / Q000196:embryology; D021041:Placental Circulation / Q000187:drug effects; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D014599:Uterus / Q000098:blood supply
chemical_list: D013267:Stilbenes; D014280:Triglycerides; D000077185:Resveratrol
keywords: Western-style diet; insulin resistance; pancreas; uterine blood flow