Abstract

While the human placenta must provide selected long-chain fatty acids to support the developing fetal brain, little is known about the mechanisms underlying the transport process. We tracked the movement of the fluorescently labeled long-chain fatty acid analogue, BODIPY-C12, across the cell layers of living explants of human term placenta. Although all layers took up the fatty acid, rapid esterification of long-chain fatty acids and incorporation into lipid droplets was exclusive to the inner layer cytotrophoblast cells rather than the expected outer syncytiotrophoblast layer. Cytotrophoblast is a progenitor cell layer previously relegated to a repair role. As isolated cytotrophoblasts differentiated into syncytialized cells in culture, they weakened their lipid processing capacity. Syncytializing cells suppress previously active genes that regulate fatty-acid uptake (SLC27A2/FATP2, FABP4, ACSL5) and lipid metabolism (GPAT3, LPCAT3). We speculate that cytotrophoblast performs a previously unrecognized role in regulating placental fatty acid uptake and metabolism.

Highlights

  • The placenta, one of nature’s most important inventions, enables the mammalian fetus to acquire maternal nutrients within the confines of the protective womb

  • We found no associations between lipid droplets (LD) volume or abundance with fetal sex in syncytiotrophoblast or cytotrophoblast

  • The presence of LD in normal placenta, led us to speculate that the syncytiotrophoblast was capable of free fatty acid esterification and that LD in cytotrophoblast originated from those manufactured in the syncytium

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Summary

Introduction

The placenta, one of nature’s most important inventions, enables the mammalian fetus to acquire maternal nutrients within the confines of the protective womb. The placenta is the tissue barrier that separates maternal and fetal bloods and is the gatekeeper for all nutrients acquired by the fetus. The placenta consists of a maternal facing layer of fused cells, the syncytiotrophoblast, an underlying layer of cytotrophoblast cells, a basal lamina, and a fetal capillary endothelium (Fig 1A). The transport of lipids across the placental barrier is less well understood than the transport of glucose[1]and amino acids[2]. While many known lipid transport proteins are expressed in PLOS ONE | DOI:10.1371/journal.pone.0153522. While many known lipid transport proteins are expressed in PLOS ONE | DOI:10.1371/journal.pone.0153522 April 28, 2016

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