Placental polar lipid composition is associated with placental gene expression and neonatal body composition

Highlights

• Placentas of different sizes have specific differences in polar lipid composition.

• Placental polar lipid composition was related to placental weight and neonatal lean mass.

• Placental polar lipid composition was related to placental gene expression.

Abstract

The polar-lipid composition of the placenta reflects its cellular heterogeneity and metabolism. This study explored relationships between placental polar-lipid composition, gene expression and neonatal body composition.

Placental tissue and maternal and offspring data were collected in the Southampton Women's Survey. Lipid and RNA were extracted from placental tissue and polar lipids measured by mass spectrometry, while gene expression was assessed using the nCounter analysis platform. Principal component analysis was used to identify patterns within placental lipid composition and these were correlated with neonatal body composition and placental gene expression.

In the analysis of placental lipids, the first three principal components explained 19.1%, 12.7% and 8.0% of variation in placental lipid composition, respectively. Principal component 2 was characterised by high principal component scores for acyl-alkyl-glycerophosphatidylcholines and lipid species containing DHA. Principal component 2 was associated with placental weight and neonatal lean mass; this component was associated with gene expression of APOE, PLIN2, FATP2, FABP4, LEP, G0S2, PNPLA2 and SRB1. Principal components 1 and 3 were not related to birth outcomes but they were associated with the gene expression of lipid related genes. Principal component 1 was associated with expression of LEP, APOE, FATP2 and ACAT2. Principal component 3 was associated with expression of PLIN2, PLIN3 and PNPLA2.

This study demonstrates that placentas of different sizes have specific differences in polar-lipid composition and related gene expression. These differences in lipid composition were associated with birth weight and neonatal lean mass, suggesting that placental lipid composition may influence prenatal lean mass accretion.

Introduction

Placental function and substrate supply are primary determinants of fetal development and have consequences for health during pregnancy and across the life course [1,2]. Polar lipid composition of the placenta may reflect multiple factors including maternal fatty acid supply, placental metabolism and placental cellular composition. These factors could affect placental function and thus the intrauterine environment and fetal development.

Polar lipids include different classes of phospholipids, sphingolipids found within the membranes and carnitines involved in lipid metabolism [3]. These lipids play important roles in the structure and function of lipid membranes. As specific lipids may be concentrated within lipid microdomains (e.g. sphingomyelins in lipid rafts [4]), within specific organelles or cell types their relative abundance may not reflect their biological importance to placental function. Fatty acids taken up by the placenta from maternal plasma may be incorporated into placental lipid pools or transported to the fetus [5,6]. Phospholipids are the major lipid pool within the placenta and there is evidence of selective partitioning of fatty acids into different placental lipid pools [7,8].

Different placental cell populations and subcellular membrane fractions have different lipid compositions which all contribute to what is measured in the lipid extracted from a tissue [9]. Changes in whole placental lipid composition may be explained by differences in cellular composition of the placenta, changes in placental lipid metabolism or altered maternal supply. The regulation of placental lipid metabolism within the placenta is not well understood, but there is evidence that it is altered in obese mothers [10,11].

This study explores how placental polar lipid composition and lipid-associated gene expression are related to birth outcomes, specifically placental weight and birthweight and neonatal body composition.