Hardy, K., Mora, J.M., Dunlop, C. et al. (3 more authors) (2018) Nuclear exclusion of SMAD2/3 in granulosa cells is associated with primordial follicle activation in the mouse ovary. Journal of Cell Science, 131 (17). jcs218123. ISSN 0021-9533
Abstract
Maintenance and activation of the limited supply of primordial follicles in the ovary are important determinants of reproductive lifespan. Currently, the molecular programme that maintains the primordial phenotype and the early events associated with follicle activation are not well defined. Here we have systematically analysed these events using microscopy and detailed image analysis. Using the immature mouse ovary as a model, we demonstrate that the onset of granulosa cell (GC) proliferation results in increased packing density on the oocyte surface and consequent GC cuboidalisation. These events precede oocyte growth and nuclear translocation of FOXO3a, a transcription factor important in follicle activation. Immunolabelling of the TGFβ signalling mediators and transcription factors, SMAD2/3, revealed a striking expression pattern specific to GCs of small follicles. SMAD2/3 was expressed in the nuclei of primordial GCs but was mostly excluded in early growing follicles. In activated follicles, GC nuclei lacking SMAD2/3 generally expressed Ki67. These findings suggest that the first phenotypic changes during follicle activation are observed in GCs, and that TGFβ signalling is fundamental for regulating GC arrest and the onset of proliferation.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2018 The Authors. Published by The Company of Biologists Ltd. This is an author produced version of a paper subsequently published in Journal of Cell Science. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Follicle; Granulosa; Primordial; SMAD; TGF-beta |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Aug 2018 09:50 |
Last Modified: | 16 Sep 2021 10:43 |
Status: | Published |
Publisher: | Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/jcs.218123 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:134879 |