Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation
Edited by R. Michael Roberts, University of Missouri-Columbia, Columbia, MO, and approved August 2, 2016 (received for review February 5, 2016)
Commentary
September 22, 2016
Significance
During pregnancy, nutrients are required for fetal growth and for the mother to maintain the pregnancy. The placenta is central to this tug-of-war over nutrients, as it is responsible for materno-fetal resource allocation. Failure to allocate resources appropriately can lead to pregnancy complications and abnormal fetal development, with long-term health consequences for both mother and baby. Here we use manipulation of a growth-regulatory protein, p110α, in mice to compare the importance of the maternal environment and genotype with fetal genotype in determining placental resource allocation. This study shows that the placenta fine-tunes the supply of maternal resources to the fetus via p110α in accordance with both the fetal drive for growth and the maternal ability to supply the required nutrients.
Abstract
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.
Acknowledgments
We thank Melanie Monk, Nuala Daw, Emma Eastwell, and staff at the Combined Animal Facility for their technical help; Dr. Gavin Jarvis for statistical advice; and Dr. Klaus Okkenhaug for providing the α/+ mice. This study was supported in part by a Centre for Trophoblast Research award of a Next Generation Fellowship (to A.N.S.-P.) and the Erasmus Exchange scheme for a scholarship (to J.L.-T.).
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Published online: September 12, 2016
Published in issue: October 4, 2016
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Acknowledgments
We thank Melanie Monk, Nuala Daw, Emma Eastwell, and staff at the Combined Animal Facility for their technical help; Dr. Gavin Jarvis for statistical advice; and Dr. Klaus Okkenhaug for providing the α/+ mice. This study was supported in part by a Centre for Trophoblast Research award of a Next Generation Fellowship (to A.N.S.-P.) and the Erasmus Exchange scheme for a scholarship (to J.L.-T.).
Notes
This article is a PNAS Direct Submission.
See Commentary on page 11066.
Authors
Competing Interests
The authors declare no conflict of interest.
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Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation, Proc. Natl. Acad. Sci. U.S.A.
113 (40) 11255-11260,
https://doi.org/10.1073/pnas.1602012113
(2016).
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