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dc.contributor.authorAykroyd, Bethany
dc.contributor.authorTunster, Simon
dc.contributor.authorSferruzzi-Perri, Amanda
dc.date.accessioned2022-02-11T00:30:51Z
dc.date.available2022-02-11T00:30:51Z
dc.date.issued2021
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333871
dc.description.abstractImprinting control region (ICR1) controls the expression of the Igf2 and H19 genes in a parent-of-origin specific manner. Appropriate expression of the Igf2-H19 locus is fundamental for normal fetal development, yet the importance of ICR1 in the placental production of hormones that promote maternal nutrient allocation to the fetus is unknown. To address this, we used a novel mouse model to selectively delete ICR1 in the endocrine junctional zone (Jz) of the mouse placenta (Jz-ΔICR1). The Jz-ΔICR1 mice exhibit increased Igf2 and decreased H19 expression specifically in the Jz. This was accompanied by an expansion of Jz endocrine cell types due to enhanced rates of proliferation and increased expression of pregnancy-specific glycoprotein 23 in the placenta of both fetal sexes. However, changes in the endocrine phenotype of the placenta were related sexually-dimorphic alterations to the abundance of IGF2 receptors and downstream signalling pathways (PI3K-AKT and MAPK). There was no effect of Jz-ΔICR1 on the expression of targets of the H19 embedded miR-675 or on fetal weight. Our results demonstrate that ICR1 controls placental endocrine capacity via sex-dependant changes in signalling. <h4>Summary statement</h4> Imprinting at Igf2-H19 ICR1 regulates endocrine cell formation and function via sexually-dimorphic changes in PI3K-AKT and MAPK signalling in the mouse.
dc.publisherCold Spring Harbor Laboratory
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleLoss of imprinting of the <i>Igf2-H19</i> ICR1 enhances placental endocrine capacity via sex-specific alterations in signalling pathways in the mouse
dc.typeArticle
dc.publisher.departmentDepartment of Physiology, Development And Neuroscience
dc.date.updated2022-02-09T14:01:01Z
dc.identifier.doi10.17863/CAM.81287
dcterms.dateAccepted2021-05-17
rioxxterms.versionofrecord10.1101/2021.05.14.444241
rioxxterms.versionVoR
dc.contributor.orcidSferruzzi-Perri, Amanda [0000-0002-4931-4233]
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-05-17
cam.depositDate2022-02-09
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International