Fetal membranes exhibit similar nutrient transporter expression profiles to the placenta

Introduction: During pregnancy, the growth of the fetus is supported by the exchange of nutrients, waste, and other molecules between maternal and fetal circulations in the utero-placental unit. Nutrient transfer, in particular, is mediated by solute transporters such as solute carrier (SLC) and adenosine triphosphate-binding cassette (ABC) proteins. While nutrient transport has been extensively studied in the placenta, the role of human fetal membranes (FM), which was recently reported to have a role in drug transport, in nutrient uptake remains unknown. Objectives: This study determined nutrient transport expression in human FM and FM cells and compared expression with placental tissues and BeWo cells. Methods: RNA sequencing (RNA-Seq) of placental and FM tissues and cells was done. Genes of major solute transporter groups, such as SLC and ABC, were identified. Proteomic analysis of cell lysates was performed via nano-liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to confirm expression at a protein level. Results: We determined that FM tissues and cells derived from the fetal membrane tissues express nutrient transporter genes, and their expression is similar to that seen in the placenta or BeWo cells. In particular, transporters involved in macronutrient and micronutrient transfer were identified in both placental and FM cells. Consistent with RNA-Seq findings, carbohydrate transporters (3), vitamin transport-related proteins (8), amino acid transporters (21), fatty acid transport-related proteins (9), cholesterol transport-related proteins (6) and nucleoside transporters (3) were identified in BeWo and FM cells, with both groups sharing similar nutrient transporter expression. Conclusion: This study determined the expression of nutrient transporters in human FMs. This knowledge is the first step in improving our understanding of nutrient uptake kinetics during pregnancy. Functional studies are required to determine the properties of nutrient transporters in human FMs.