ABSTRACT
The phosphoinositide 3-kinase (PI3K)/Akt pathway is thought to regulate key steps of mammalian oogenesis, such as dormant oocyte awakening during follicular activation, meiotic resumption and oocyte maturation. Supporting evidence is, however, indirect, as oocyte PI3K activation has never been formally demonstrated, and the PI3K isoforms involved have not been revealed. Here, we employed fluorescent PIP3 biosensors to characterize PI3K dynamics in mouse oocytes and we investigated the contribution of the PI3K isoform p110α by conditional genetic ablation. Prophase oocytes showed baseline PI3K/Akt activation that could be further stimulated by adding Kit ligand. Contrary to previous reports, maternal PI3K proved dispensable for oocyte maturation in vitro, yet it was required for PIP3 synthesis in early embryos. We further show that oocyte p110α is not essential for oogenesis and female fertility. Accordingly, our data suggest that Kit ligand activates isoform p110δ for PIP3 synthesis in oocytes. In contrast, constitutive PIP3 synthesis in early embryos is achieved by maternal p110α acting redundantly with p110δ. This study highlights the relevance of PIP3 biosensors in establishing the dynamics, mechanisms and roles of maternal PI3K signaling during mammalian oogenesis.
Footnotes
Author contributions
Conceptualization: G.H.; Data curation: A.B., G.H.; Formal analysis: A.B., P.V., J.B., G.H.; Funding acquisition: J.G.-G., J.C., G.H.; Investigation: A.B., P.V., J.B., C.S., D.G., G.H.; Methodology: A.B., P.V., N.T., J.G.-G., G.H.; Project administration: G.H.; Resources: J.G.-G., J.C., G.H.; Supervision: G.H.; Validation: A.B., P.V., J.B., C.S., D.G., G.H.; Visualization: A.B., P.V., J.B., G.H.; Writing – original draft: G.H.
Funding
This work was supported by Centre National de la Recherche Scientifique (CNRS; G.H.), Agence de la Biomédecine (G.H.), Région Bretagne (G.H.), the UK Medical Research Council (J.C.) and Fondation ARC pour la Recherche sur le Cancer (ARCPGA2022120005630_6362 to J.G.-G.).
Data availability
All relevant data can be found within the article and its supplementary information.
