Expression of cholesterol packaging and transport genes in human and rat placenta: impact of obesity and a high-fat diet

J Dev Orig Health Dis. 2020 Jun;11(3):222-227. doi: 10.1017/S2040174419000606. Epub 2019 Oct 11.

Abstract

Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspring. We have previously shown that exposure to a low-protein diet during gestation was associated with upregulation of genes associated with cholesterol transport and packaging within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6) to alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. The potential for maternal body mass index (BMI) to be associated with expression of these genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20-day gestation (term = 21-22-day gestation) that had been fed one of four diets containing varying fatty acid compositions during pregnancy, and from 62 women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and transfer was assessed in rodent and human samples by quantitative real time polymerase chain reaction. In rats, placental mRNA expression of ApoA2, ApoC2, Cubn, Fgg, Mttp and Ttr was significantly elevated (3-30 fold) in animals fed a high LA (36% fat) diet, suggesting increased cholesterol transport across the placenta in this group. In women, maternal BMI was associated with fewer inconsistent alterations in gene expression. In summary, sub-optimal maternal nutrition is associated with alterations in the expression of genes associated with cholesterol transport in a rat model. This may contribute to altered fetal development and potentially programme disease risk in later life. Further investigation of human placenta in response to specific dietary interventions is required.

Keywords: Cholesterol; maternal nutrition; omega; placenta; pregnancy.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cholesterol / metabolism
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Female
  • Fetal Development / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Humans
  • Linoleic Acid / administration & dosage
  • Linoleic Acid / adverse effects
  • Maternal Nutritional Physiological Phenomena / genetics*
  • Obesity / complications*
  • Obesity / metabolism
  • Placenta / metabolism*
  • Pregnancy
  • Rats
  • Real-Time Polymerase Chain Reaction
  • alpha-Linolenic Acid / administration & dosage
  • alpha-Linolenic Acid / adverse effects

Substances

  • alpha-Linolenic Acid
  • Cholesterol
  • Linoleic Acid