title: Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition.
abstract: Prepregnancy maternal obesity confers an increased risk of stillbirth, but the mechanisms are unknown. Maternal obesity is associated with placental inflammation. We considered that maternal diet may predispose to the increased risk of placental inflammation and stillbirth. We hypothesized that a chronic high-fat diet (HFD) is associated with abnormal uteroplacental circulation and placental inflammation. Here we used a nonhuman primate model to determine the effect of chronic HFD on the uterine and placental hemodynamics, placental histology, and inflammation in a prospective, observational study of 24 Japanese macaques. Overall, there was a statistically significant (38-56%) reduction in uterine volume blood flow from HFD animals, whether they were lean or obese. Consumption of a HFD, independent of obesity, increased placental inflammatory cytokines and the expression of Toll-like receptor 4. We show that HFD consumption by obese mothers with hyperinsulinemia also reduced volume blood flow on the fetal side of the placenta and significantly increased the frequency of both placental infarctions and stillbirth. These results suggest that a HFD, independent of obesity, decreases uterine volume blood flow. Maternal obesity and insulin resistance further exacerbates the placental dysfunction and results in an increased frequency of stillbirth.
authors: Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, USA. friasa@ohsu.edu
authors: Antonio E
authors: AE
authors: Frias
authors: Terry K
authors: TK
authors: Morgan
authors: Anne E
authors: AE
authors: Evans
authors: Juha
authors: J
authors: Rasanen
authors: Karen Y
authors: KY
authors: Oh
authors: Kent L
authors: KL
authors: Thornburg
authors: Kevin L
authors: KL
authors: Grove
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004041:Dietary Fats / Q000009:adverse effects* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008251:Macaca; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D010920:Placenta / Q000098:blood supply* / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D039401:Prenatal Nutritional Physiological Phenomena; D012039:Regional Blood Flow; D050497:Stillbirth / Q000453:epidemiology*; D014599:Uterus / Q000098:blood supply* / Q000276:immunology
chemical_list: D016207:Cytokines; D004041:Dietary Fats