Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation.
Pregnancy success and life-long health depend on a cooperative interaction between the mother and the fetus in the allocation of resources. As the site of materno-fetal nutrient transfer, the placenta is central to this interplay; however, the relative importance of the maternal versus fetal genotypes in modifying the allocation of resources to the fetus is unknown. Using genetic inactivation of the growth and metabolism regulator, Pik3ca (encoding PIK3CA also known as p110α, α/+), we examined the interplay between the maternal genome and the fetal genome on placental phenotype in litters of mixed genotype generated through reciprocal crosses of WT and α/+ mice. We demonstrate that placental growth and structure were impaired and associated with reduced growth of α/+ fetuses. Despite its defective development, the α/+ placenta adapted functionally to increase the supply of maternal glucose and amino acid to the fetus. The specific nature of these changes, however, depended on whether the mother was α/+ or WT and related to alterations in endocrine and metabolic profile induced by maternal p110α deficiency. Our findings thus show that the maternal genotype and environment programs placental growth and function and identify the placenta as critical in integrating both intrinsic and extrinsic signals governing materno-fetal resource allocation.
Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom; ans48@cam.ac.uk.
Amanda N
AN
Sferruzzi-Perri
Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom.
Jorge
J
López-Tello
Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom.
Abigail L
AL
Fowden
Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom; Metabolic Research Laboratories, Medical Research Council Metabolic Diseases Unit, Department of Obstetrics and Gynaecology, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge CB2 0SW, United Kingdom.
Miguel
M
Constancia
D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001835:Body Weight; D019070:Cell Lineage / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases / Q000172:deficiency / Q000378:metabolism*; D004703:Endocrine System / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D008099:Liver / Q000033:anatomy & histology; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D055432:Metabolomics; D018345:Mice, Knockout; D008954:Models, Biological; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000378:metabolism
D015091:beta-Alanine; D019325:3-O-Methylglucose; C012924:2,2-dimethyl-beta-alanine; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases
PI3K; fetus; nutrient transport; placenta; resource allocation