Back to Search
Start Over
Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice.
- Source :
-
Clinical science (London, England : 1979) [Clin Sci (Lond)] 2021 Sep 17; Vol. 135 (17), pp. 2049-2066. - Publication Year :
- 2021
-
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.<br /> (© 2021 The Author(s).)
- Subjects :
- Amino Acid Transport System A genetics
Animals
Case-Control Studies
Female
Fetal Growth Retardation genetics
Fetal Growth Retardation physiopathology
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Placenta physiopathology
Pregnancy
Prospective Studies
RNA Interference
Amino Acid Transport System A deficiency
Fetal Development
Fetal Growth Retardation metabolism
Placenta metabolism
Placentation
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8736
- Volume :
- 135
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Clinical science (London, England : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 34406367
- Full Text :
- https://doi.org/10.1042/CS20210575