Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems.
The mammalian fetus is unique in its dependence during gestation on the supply of maternal nutrients through the placenta. Maternal supply and fetal demand for nutrients need to be fine tuned for healthy growth and development of the fetus along its genetic trajectory. An altered balance between supply and demand can lead to deviations from this trajectory with long-term consequences for health. We have previously shown that in a knockout lacking the imprinted placental-specific Igf2 transcript (P0), growth of the placenta is compromised from early gestation but fetal growth is normal until late gestation, suggesting functional adaptation of the placenta to meet the fetal demands. Here, we show that placental transport of glucose and amino acids are increased in the Igf2 P0(+/-) null and that this up-regulation of transport occurs, at least in part, through increased expression of the transporter genes Slc2a3 and Slc38a4, the imprinted member of the System A amino acid transporter gene family. Decreasing fetal demand genetically by removal of fetal Igf2 abolished up-regulation of both transport systems and reduced placental System A amino acid transport activity and expression of Slc38a2 in late gestation. Our results provide direct evidence that the placenta can respond to fetal demand signals through regulation of expression of specific placental transport systems. Thus, crosstalk between an imprinted growth demand gene (Igf2) and placental supply transporter genes (Slc38a4, Slc38a2, and Slc2a3) may be a component of the genetic control of nutrient supply and demand during mammalian development.
Constância
Miguel
M
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, United Kingdom. miguel.constancia@bbsrc.ac.uk
Angiolini
Emily
E
Sandovici
Ionel
I
Smith
Paul
P
Smith
Rachel
R
Kelsey
Gavin
G
Dean
Wendy
W
Ferguson-Smith
Anne
A
Sibley
Colin P
CP
Reik
Wolf
W
Fowden
Abigail
A
D000483:Alleles; D026924:Amino Acid Transport System A / Q000235:genetics; D026905:Amino Acid Transport Systems / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D005260:Female; D005333:Fetus / Q000378:metabolism*; D017353:Gene Deletion; D018392:Genomic Imprinting; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism / Q000502:physiology*; D007335:Insulin-Like Growth Factor II; D007763:Lac Operon; D026901:Membrane Transport Proteins / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009154:Mutation; D010920:Placenta / Q000378:metabolism*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D019076:Transgenes; D015854:Up-Regulation
D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems; D051246:Glucose Transport Proteins, Facilitative; D051274:Glucose Transporter Type 3; C035170:IGF2 protein, human; D026901:Membrane Transport Proteins; D011506:Proteins; D012333:RNA, Messenger; C498798:Slc38a2 protein, mouse; D007335:Insulin-Like Growth Factor II; D005947:Glucose