GDF9 is transiently expressed in oocytes before follicle formation in the human fetal ovary and is regulated by a novel NOBOX transcript
Author(s)
Type
Journal Article
Abstract
During human fetal ovary development, the process of primordial follicle formation is immediately preceded by a highly dynamic period of germ cell and somatic cell reorganisation. This is regulated by germ-cell specific transcription regulators, by the conserved RNA binding proteins DAZL and BOLL and by secreted growth factors of the TGFβ family, including activin βA: these all show changing patterns of expression preceding follicle formation. In mice, the transcription factor Nobox is essential for follicle formation and oocyte survival, and NOBOX regulates the expression of GDF9 in humans. We have therefore characterised the expression of GDF9 in relation to these known key factors during follicle formation in the human fetal ovary. mRNA levels of GDF9, BMP15 and NOBOX were quantified by qRT-PCR and showed dramatic increases across gestation. GDF9 protein expression was localised by immunohistochemistry to the same population of germ cells as those expressing activin βA prior to follicle formation but did not co-localise with either BOLL or DAZL. A novel NOBOX isoform was identified in fetal ovary that was shown to be capable of up-regulating the GDF9 promoter in reporter assays. Thus, during oogenesis in humans, oocytes go through a dynamic and very sharply demarcated sequence of changes in expression of these various proteins, even within individual germ cell nests, likely to be of major functional significance in determining selective germ cell survival at this key stage in ovarian development. Transcriptional variation may contribute to the range of age of onset of POI in women with NOBOX mutations.
Date Issued
2015-03-19
Date Acceptance
2015-01-16
Citation
PLoS ONE, 2015, 10 (3)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS ONE
Volume
10
Issue
3
Copyright Statement
© 2015 Bayne et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
access article distributed under the terms of the
Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000351425400108&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GROWTH-DIFFERENTIATION FACTOR-9
BONE MORPHOGENETIC PROTEIN-15
GERM-CELLS
GENE-EXPRESSION
SOMATIC-CELLS
DNA
FOLLICULOGENESIS
INITIATION
MUTATIONS
RECEPTORS
Publication Status
Published
Article Number
e0119819
Date Publish Online
2015-03-19