Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in mice
Studies suggest that placental nutrient supply adapts according to fetal demands. However, signaling events underlying placental adaptations remain unknown. Here we demonstrate that phosphoinositide 3-kinase p110α in the fetus and the trophoblast interplay to regulate placental nutrient supply and f...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/45282 |
| _version_ | 1811180935488471040 |
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| author | Jorge López-Tello Vicente Pérez-García Jaspreet Khaira Laura C Kusinski Wendy N Cooper Adam Andreani Imogen Grant Edurne Fernández de Liger Brian YH Lam Myriam Hemberger Ionel Sandovici Miguel Constancia Amanda N Sferruzzi-Perri |
| author_facet | Jorge López-Tello Vicente Pérez-García Jaspreet Khaira Laura C Kusinski Wendy N Cooper Adam Andreani Imogen Grant Edurne Fernández de Liger Brian YH Lam Myriam Hemberger Ionel Sandovici Miguel Constancia Amanda N Sferruzzi-Perri |
| author_sort | Jorge López-Tello |
| collection | DOAJ |
| description | Studies suggest that placental nutrient supply adapts according to fetal demands. However, signaling events underlying placental adaptations remain unknown. Here we demonstrate that phosphoinositide 3-kinase p110α in the fetus and the trophoblast interplay to regulate placental nutrient supply and fetal growth. Complete loss of fetal p110α caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and impaired placental formation and nutrient transport. Loss of trophoblast p110α resulted in viable fetuses, abnormal placental development and a failure of the placenta to transport sufficient nutrients to match fetal demands for growth. Using RNA-seq we identified genes downstream of p110α in the trophoblast that are important in adapting placental phenotype. Using CRISPR/Cas9 we showed loss of p110α differentially affects gene expression in trophoblast and embryonic stem cells. Our findings reveal important, but distinct roles for p110α in the different compartments of the conceptus, which control fetal resource acquisition and growth. |
| first_indexed | 2024-04-11T09:11:40Z |
| format | Article |
| id | doaj.art-57db7a58e0f24f85a79ce8d6453f5b04 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:11:40Z |
| publishDate | 2019-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-57db7a58e0f24f85a79ce8d6453f5b042022-12-22T04:32:29ZengeLife Sciences Publications LtdeLife2050-084X2019-06-01810.7554/eLife.45282Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in miceJorge López-Tello0https://orcid.org/0000-0002-7886-0233Vicente Pérez-García1Jaspreet Khaira2Laura C Kusinski3Wendy N Cooper4https://orcid.org/0000-0003-3416-9982Adam Andreani5Imogen Grant6Edurne Fernández de Liger7Brian YH Lam8Myriam Hemberger9Ionel Sandovici10https://orcid.org/0000-0001-5674-4269Miguel Constancia11Amanda N Sferruzzi-Perri12https://orcid.org/0000-0002-4931-4233Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; Epigenetics Programme, The Babraham Institute, Cambridge, United KingdomCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics and Gynaecology, The Rosie Hospital, Cambridge, United KingdomMetabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics and Gynaecology, The Rosie Hospital, Cambridge, United KingdomCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomMetabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics and Gynaecology, The Rosie Hospital, Cambridge, United KingdomEpigenetics Programme, The Babraham Institute, Cambridge, United Kingdom; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, CanadaCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics and Gynaecology, The Rosie Hospital, Cambridge, United KingdomCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Department of Obstetrics and Gynaecology, The Rosie Hospital, Cambridge, United KingdomCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomStudies suggest that placental nutrient supply adapts according to fetal demands. However, signaling events underlying placental adaptations remain unknown. Here we demonstrate that phosphoinositide 3-kinase p110α in the fetus and the trophoblast interplay to regulate placental nutrient supply and fetal growth. Complete loss of fetal p110α caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and impaired placental formation and nutrient transport. Loss of trophoblast p110α resulted in viable fetuses, abnormal placental development and a failure of the placenta to transport sufficient nutrients to match fetal demands for growth. Using RNA-seq we identified genes downstream of p110α in the trophoblast that are important in adapting placental phenotype. Using CRISPR/Cas9 we showed loss of p110α differentially affects gene expression in trophoblast and embryonic stem cells. Our findings reveal important, but distinct roles for p110α in the different compartments of the conceptus, which control fetal resource acquisition and growth.https://elifesciences.org/articles/45282placentapregnancyresource allocationnutrient transportPI3Kfetus |
| spellingShingle | Jorge López-Tello Vicente Pérez-García Jaspreet Khaira Laura C Kusinski Wendy N Cooper Adam Andreani Imogen Grant Edurne Fernández de Liger Brian YH Lam Myriam Hemberger Ionel Sandovici Miguel Constancia Amanda N Sferruzzi-Perri Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in mice eLife placenta pregnancy resource allocation nutrient transport PI3K fetus |
| title | Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in mice |
| title_full | Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in mice |
| title_fullStr | Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in mice |
| title_full_unstemmed | Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in mice |
| title_short | Fetal and trophoblast PI3K p110α have distinct roles in regulating resource supply to the growing fetus in mice |
| title_sort | fetal and trophoblast pi3k p110α have distinct roles in regulating resource supply to the growing fetus in mice |
| topic | placenta pregnancy resource allocation nutrient transport PI3K fetus |
| url | https://elifesciences.org/articles/45282 |
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