Article Figures & Data
Figures
- Fig. 1.
Overview of amino acid transport systems in the placenta. Exchangers, accumulative, and facilitative transporters work in concert to drive a net transfer of amino acids from maternal to fetal circulation. Examples of transporters in each transport category are provided along with their speculated localization in humans on either the maternal-facing microvillous membrane or fetal-facing basolateral membrane. BAT: bidirectional amino acid transporter; TAT1: T-type amino acid transporter 1. 4F2hc covalently links to members of the SLC7A6 and SLC7A7 families, including LAT1 and LAT2, to form heteromeric amino acid transporters. Y + L amino acid transporters (y + LATs) belong to the y + L system of amino acid transporters that transports both neutral and basic amino acids.
Tables
- TABLE 1
Summary of studies examining the impact of inflammation on amino acid transporter expression in the placenta
Amino acid substrates are taken from Cleal et al., 2018 unless otherwise specified. Drug substrates are italicized and taken from Zhang et al., 2020. ↑ signifies increased expression, ↓ signifies decreased expression, ↔ signifies no change in expression, and X signifies that expression was not assessed. When possible, the approximate magnitude of change is provided as percent increase or decrease. (F) denotes a change in female placentas, (M) denotes a change in male placentas.
Transporter Substrates Model Condition/Treatment mRNA Protein Reference EAAT2
(SLC1A2)Aspartate, glutamate Rats Poly(I:C) ↔ ↓45% (McColl and Piquette‐Miller, 2019) ASCT1
(SLC1A4)Alanine, serine, cysteine, threonine Mice Pre-eclampsia ↔ X (Stojanovska et al., 2019) Rats Poly(I:C) ↑90% ↓75% (McColl and Piquette‐Miller, 2019) Horses Ascending placentitis ↓ X (El-Sheikh Ali et al., 2021) ASCT2
(SLC1A5)Alanine, serine, cysteine, glutamine, threonine, asparagine Human chorionic plate arteries Pre-eclampsia (plus TNF-α and IFN-γ) ↔ X (Broekhuizen et al., 2020) Humans Pre-eclampsia X ↔ (Aiko et al., 2014) ↔ X (Chen et al., 2006) 4F2hc
(SLC3A2)Chaperone subunit for LAT1 and LAT2 Humans Pre-eclampsia X ↑25% (Aiko et al., 2014) Mice Pre-eclampsia ↔ X (Stojanovska et al., 2019) Malaria ↓65% X (Najjar et al., 2019) Rats Poly(I:C) ↑50% X (McColl and Piquette‐Miller, 2019) Horses Ascending placentitis ↓ X (El-Sheikh Ali et al., 2021) TAUT
(SLC6A6)Taurine Rats Poly(I:C) ↑75% ↑75% (McColl and Piquette‐Miller, 2019) CAT1
(SLC7A1)Arginine, histidine, lysine Mice Malaria ↓70% X (Najjar et al., 2019) CAT2
(SLC7A2)Arginine, histidine, lysine HUVEC TNF-α ↑380% X (Knyazev et al., 2017) Rats Poly(I:C) ↑40% X (McColl and Piquette‐Miller, 2019) CAT3
(SLC7A3)Arginine, histidine, lysine Mice Preimplantation genetic diagnosis ↓30% ↓60% (Yao et al., 2016) LAT1
(SLC7A5)Leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine, histidine, L-DOPA, melphalan, baclofen, gabapentin Humans Pre-eclampsia X ↑ (Aiko et al., 2014) Human chorionic plate arteries Pre-eclampsia (plus TNF-α and IFN-γ) ↔ X (Broekhuizen et al., 2020) Mice Malaria ↓80% X (Najjar et al., 2019) LAT2
(SLC7A8)Leucine, isoleucine, valine, alanine, serine, threonine, cysteine, phenylalanine, tyrosine, tryptophan, asparagine, histidine, methionine, glutamine, glycine Human chorionic plate arteries Pre-eclampsia (plus TNF-α and IFN-γ) ↔ X (Broekhuizen et al., 2020) Mice Preimplantation genetic diagnosis ↓25% X (Yao et al., 2016) BAT1
(SLC7A9)Arginine, histidine, lysine, phenylalanine, tyrosine, tryptophan, threonine, methionine, valine, isoleucine, leucine Horses Ascending placentitis ↓ X (El-Sheikh Ali et al., 2021) SNAT1
(SLC38A1)Glutamine, alanine, asparagine, cysteine, histidine, serine Primary human trophoblasts TNF-α ↔ ↑70-80% (Jones et al., 2009; Aye et al., 2015) IL-6 ↔ ↑80% (Jones et al., 2009) Poly(I:C) ↑50% ↑45% (Liong and Lappas, 2017) LPS ↑160% ↑60% BeWo-b30 cells (M) IL-1β ↓40% X (Thongsong et al., 2005) Human placentas Malaria ↓50% X (Boeuf et al., 2013) Mice Preimplantation genetic diagnosis ↓20% X (Yao et al., 2016) Pre-eclampsia ↓50% (F)
↔ (M)X (Stojanovska et al., 2019) Rats Poly(I:C) ↑35% X (McColl and Piquette‐Miller, 2019) SNAT2
(SLC38A2)Alanine, asparagine, cysteine, glutamine, glycine, histidine, methionine, proline, serine Primary human trophoblasts TNF-α ↑50% ↑70% (Jones et al., 2009) ↔ ↑70% (Aye et al., 2015) IL-6 ↑80% ↑55% (Jones et al., 2009) Poly(I:C) ↑100% X (Liong and Lappas, 2017) LPS ↑100% X BeWo-b30 cells (M) IL-1β ↓15% X (Thongsong et al., 2005) Human placentas Malaria ↓50% (trend) X (Boeuf et al., 2013) Primary murine trophoblasts TNF-α ↓40% X (Claycombe-Larson et al., 2020) IL-1β ↔ X Mice Pre-eclampsia ↔ X (Stojanovska et al., 2019) Rats Poly(I:C) ↑30% ↓20% (trend) (McColl and Piquette‐Miller, 2019) SNAT4
(SLC38A4)Alanine, asparagine, cysteine, glycine, serine, threonine Primary human trophoblasts TNF-α ↔ ↔ (Jones et al., 2009; Aye et al., 2015) IL-6 ↔ ↔ (Jones et al., 2009) Mice PE ↔ X (Stojanovska et al., 2019) SNAT5
(SLC38A5)Glutamine, histidine, asparagine, serine Humans Pre-eclampsia (with or without IUGR) X ↔ (Huang et al., 2018) SNAT7
(SLC38A7)Glutamine, histidine, alanine, serine, asparagine (Hagglund et al., 2011) Horses Ascending placentitis ↓ X (El-Sheikh Ali et al., 2021) HUVEC human umbilical vein endothelial cell; IUGR, intrauterine growth restriction.
