- Title
- Transcriptomic profiling of neonatal mouse granulosa cells reveals new insights into primordial follicle activation
- Creator
- Ford, Emmalee A.; Frost, Emily R.; Beckett, Emma L.; Roman, Shaun D.; McLaughlin, Eileen A.; Sutherland, Jessie M.
- Relation
- Biology of Reproduction Vol. 106, Issue 3, p. 503-514
- Publisher Link
- http://dx.doi.org/10.1093/biolre/ioab193
- Publisher
- Oxford University Press
- Resource Type
- journal article
- Date
- 2022
- Description
- The dormant population of ovarian primordial follicles is determined at birth and serves as the reservoir for future female fertility. Yet our understanding of the molecular, biochemical, and cellular processes underpinning primordial follicle activation remains limited. The survival of primordial follicles relies on the correct complement and morphology of granulosa cells, which provide signaling factors essential for oocyte and follicular survival. To investigate the contribution of granulosa cells in the primordial-to-primary follicle transition, gene expression profiles of granulosa cells undergoing early differentiation were assessed in a murine model. Ovaries from C57Bl/6 mice were enzymatically dissociated at time-points spanning the initial wave of primordial follicle activation. Post-natal day (PND) 1 ovaries yielded primordial granulosa cells, and PND4 ovaries yielded a mixed population of primordial and primary granulosa cells. The comparative transcriptome of granulosa cells at these time-points was generated via Illumina NextSeq 500 system, which identified 131 significantly differentially expressed transcripts. The differential expression of eight of the transcripts was confirmed by RT-qPCR. Following biological network mapping via Ingenuity Pathway Analysis, the functional expression of the protein products of three of the differentially expressed genes, namely FRZB, POD1, and ZFX, was investigated with in-situ immunolocalization in PND4 mouse ovaries was investigated. Finally, evidence was provided that Wnt pathway antagonist, secreted frizzled-related protein 3 (FRZB), interacts with a suppressor of primordial follicle activation WNT3A and may be involved in promoting primordial follicle activation. This study highlights the dynamic changes in gene expression of granulosa cells during primordial follicle activation and provides evidence for a renewed focus into the Wnt signaling pathway's role in primordial follicle activation.
- Subject
- folliculogenesis; granulosa cells; RNAseq; infertility; premature ovarian insufficiency; SDG 7; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1463778
- Identifier
- uon:46833
- Identifier
- ISSN:0006-3363
- Rights
- © The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
- Language
- eng
- Full Text
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