Human placental uptake of glutamine and glutamate is reduced in fetal growth restriction

Area of Science:

• Obstetrics and Gynecology
• Fetal Medicine
• Molecular Biology

Background:

• Fetal growth restriction (FGR) increases risks for stillbirth and neonatal complications.
• FGR placentas are smaller with reduced amino acid transporter activity compared to appropriate for gestational age (AGA) infants.
• The role of glutamine and glutamate transport in FGR placental dysfunction is not well understood.

Purpose of the Study:

• To investigate if FGR is associated with altered placental transport and expression of glutamine and glutamate.
• To explore the mammalian target of rapamycin (mTOR) signaling pathway as a potential mechanism regulating these transporters in FGR.

Main Methods:

• Comparison of placental characteristics and amino acid uptake in FGR infants (IBR < 5th centile) versus AGA infants (IBR 20th-80th).
• Measurement of 14C-glutamine and 14C-glutamate uptake rates per mg of placental protein.
• Assessment of key transporter protein expression (LAT1, LAT2, SNAT5 for glutamine; EAAT1 for glutamate).
• In vitro experiments exposing placental tissue from uncomplicated pregnancies to rapamycin to assess mTOR pathway influence.

Main Results:

• FGR placentas were lighter and showed reduced initial uptake rates of 14C-glutamine and 14C-glutamate.
• Despite reduced uptake, key transporter protein expression (LAT1, LAT2, SNAT5, EAAT1) was higher in FGR placentas.
• In vitro rapamycin exposure inhibited placental glutamine and glutamate uptake, implicating mTOR in transport regulation.

Conclusions:

• FGR is associated with reduced placental transport activity for glutamine and glutamate.
• Abnormal amino acid transporter activity is a component of placental dysfunction in FGR.
• The mTOR pathway plays a role in regulating placental transport of glutamine and glutamate, suggesting it as a potential therapeutic target in FGR.