Vaughan, OR;
Maksym, K;
Silva, E;
Barentsen, K;
Anthony, RV;
Brown, TL;
Hillman, SL;
... Jansson, T; + view all
(2021)
Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice.
Clinical science
, 135
(17)
pp. 2049-2066.
10.1042/cs20210575.
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Abstract
Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane (TPM) SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid (MeAIB). We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared with appropriate for gestational age (AGA) control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes FGR and could be a target for clinical therapies for late-onset FGR.
| Type: | Article |
|---|---|
| Title: | Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1042/cs20210575 |
| Publisher version: | http://dx.doi.org/10.1042/cs20210575 |
| Language: | English |
| Additional information: | © 2021 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). |
| Keywords: | amino acid transport system A, fetal growth restriction, lentivirus, maternal-fetal exchange, MeAIB, syncytiotrophoblast |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10134431 |
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