Back to Search
Start Over
Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice
- Source :
- Clinical Science (London, England : 1979)
- Publication Year :
- 2021
- Publisher :
- Portland Press, 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.
- Subjects :
- Amino Acid Transport System A
Placenta
syncytiotrophoblast
Biology
Molecular Bases of Health & Disease
fetal growth restriction
Fetal Development
Andrology
Small hairpin RNA
Syncytiotrophoblast
lentivirus
Pregnancy
Gene expression
medicine
Animals
Prospective Studies
Research Articles
Fetus
Gene knockdown
Fetal Growth Retardation
Fetal viability
maternal-fetal exchange
MeAIB
Gene Expression Regulation, Developmental
Trophoblast
General Medicine
Placentation
Metabolism
medicine.anatomical_structure
Case-Control Studies
Gene Knockdown Techniques
embryonic structures
Female
RNA Interference
Cell Membranes, Excitation & Transport
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 01435221
- Database :
- OpenAIRE
- Journal :
- Clinical Science (London, England : 1979)
- Accession number :
- edsair.doi.dedup.....69dd9c300d3a9dc565c9ee95b97d56b4