Trophic signals acting via phosphatidylinositol-3 kinase are required for normal pre-implantation mouse embryo development

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dc.contributor.authorLu, D.P.
dc.contributor.authorChandrakanthan, V.
dc.contributor.authorCahana, A.
dc.contributor.authorIshii, S.
dc.contributor.authorO'Neill, C.
dc.date.issued2004
dc.description.abstractThe growth and survival of the preimplantation mammalian embryo may be regulated by several autocrine trophic factors that have redundant or overlapping actions. One of the earliest trophic factors to be produced is embryo-derived platelet-activating factor (1-O-alky-2- acetyl-sn-glyceryl-3-phosphocholine). The addition of platelet-activating factor to embryo culture media exerted a trophic effect, but structurally related lipids (3-O-alky-2- acetyl-sn-glyceryl-1-phosphocholine, 1-O-alky-sn-glyceryl- 3-phosphocholine, octadecyl-phosphocholine) had no effect. Platelet-activating factor induced a pertussis toxinsensitive [Ca²⁺]i transient in two-cell embryos that did not occur in platelet-activating factor-receptor null (Pafr–/–) genotype embryos. Fewer Pafr–/– mouse zygotes developed to the blastocyst stage in vitro compared with Pafr+/+ zygotes (P<0.02), those that developed to blastocysts had fewer cells (P<0.001) and more cells with fragmented nuclei (P<0.001). The inhibition of 1-O-phosphatidylinositol 3- kinase (LY294002 (3 μM and 15 μM) and wortmannin (10 nM and 50 nM)) caused a dose-dependent inhibition of platelet-activating factor-induced [Ca²⁺]i transients (P<0.001). The two-cell embryo expressed 1-Ophosphatidylinositol 3-kinase catalytic subunits p110α, β, γ and δ, and regulatory subunits p85α and β. LY294002 and wortmannin each caused a significant reduction in the proportion of embryos developing to the morula and blastocyst stages in vitro, reduced the number of cells within each blastocyst, and significantly increased the proportion of cells in blastocysts with fragmented nuclei. The results indicate that embryo-derived plateletactivating factor (and other embryotrophic factors) act through its membrane receptor to enhance embryo survival through a 1-O-phosphatidylinositol 3-kinase-dependent survival pathway.
dc.description.statementofresponsibilityD. P. Lu, V. Chandrakanthan, A. Cahana, S. Ishii, and C. O'Neill
dc.identifier.citationJournal of Cell Science, 2004; 117(8):1567-1576
dc.identifier.doi10.1242/jcs.00991
dc.identifier.issn0021-9533
dc.identifier.issn1477-9137
dc.identifier.orcidChandrakanthan, V. [0000-0002-4314-5029]
dc.identifier.urihttps://hdl.handle.net/2440/145942
dc.language.isoen
dc.publisherThe Company of Biologists
dc.rights© The Company of Biologists Limited 2004
dc.source.urihttps://doi.org/10.1242/jcs.00991
dc.subjectPAF; PAF-receptor; Phosphatidylinositol 3-kinase; Calcium signalling; Preimplantation embryo
dc.subject.meshZygote
dc.subject.meshBlastocyst
dc.subject.meshMorula
dc.subject.meshAnimals
dc.subject.meshMice, Knockout
dc.subject.meshMice
dc.subject.meshMorpholines
dc.subject.meshChromones
dc.subject.meshAndrostadienes
dc.subject.meshPlatelet Activating Factor
dc.subject.meshPlatelet Membrane Glycoproteins
dc.subject.meshReceptors, G-Protein-Coupled
dc.subject.meshRNA, Messenger
dc.subject.meshEnzyme Inhibitors
dc.subject.meshCulture Media
dc.subject.meshCulture Techniques
dc.subject.meshCalcium Signaling
dc.subject.meshEmbryonic Development
dc.subject.meshPregnancy
dc.subject.meshDose-Response Relationship, Drug
dc.subject.meshFemale
dc.subject.meshPhosphatidylinositol 3-Kinases
dc.subject.meshWortmannin
dc.titleTrophic signals acting via phosphatidylinositol-3 kinase are required for normal pre-implantation mouse embryo development
dc.typeJournal article
pubs.publication-statusPublished

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