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Somatic Cells Initiate Primordial Follicle Activation and Govern the Development of Dormant Oocytes in Mice

Journal article
Authors Hua Zhang
Sanjiv Risal
Nagaraju Gorre
Kiran Busayavalasa
Xin Li
Yan Shen
B. Bosbach
Mats Brännström
Kui Liu
Published in Current Biology
Volume 24
Issue 21
Pages 2501-2508
ISSN 0960-9822
Publication year 2014
Published at Department of Chemistry and Molecular Biology
Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Pages 2501-2508
Language en
Subject categories Biochemistry and Molecular Biology, Cell Biology


Background: The majority of oocytes in the mammalian ovary are dormant oocytes that are enclosed in primordial follicles by several somatic cells, which we refer to as primordial follicle granulosa cells (pfGCs). Very little is known, however, about how the pfGCs control the activation of primordial follicles and the developmental fates of dormant oocytes. Results: By targeting molecules in pfGCs with several mutant mouse models, we demonstrate that the somatic pfGCs initiate the activation of primordial follicles and govern the quiescence or awakening of dormant oocytes. Inhibition of mTORC1 signaling in pfGCs prevents the differentiation of pfGCs into granulosa cells, and this arrests the dormant oocytes in their quiescent states, leading to oocyte death. Overactivation of mTORC1 signaling in pfGCs accelerates the differentiation of pfGCs into granulosa cells and causes premature activation of all dormant oocytes and primordial follicles. We further show that pfGCs trigger the awakening of dormant oocytes through KIT ligand (KITL), and we present an essential communication network between the somatic cells and germ cells that is based on signaling between the mTORC1-KITL cascade in pfGCs and KIT-PI3K signaling in oocytes. Conclusions: Our findings provide a relatively complete picture of how mammalian primordial follicles are activated. The microenvironment surrounding primordial follicles can activate mTORC1-KITL signaling in pfGCs, and these cells trigger the awakening of dormant oocytes and complete the process of follicular activation. Such communication between the microenvironment, somatic cells, and germ cells is essential to maintaining the proper reproductive lifespan in mammals.

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