PXD003283 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Oviductal fluid LC-MS/MS - The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis |
Description | After fertilization the developing mammalian embryo migrates through the oviduct before it implants in the uterus. In order to prevent tubal pregnancy or failed implantation, development and migration of the embryo has to be tightly coordinated1. The precise molecular basis for the regulation of this maternal-embryonic interaction is largely unknown. Here we show that the Wilms tumor suppressor protein Wt1 is a critical regulator of the interaction between the maternal environment and the early embryo. Our results indicate that subfertility in Wt1ko/+ females is a maternal effect caused by the Wt1-dependent de-regulation of Prss29, encoding a serine protease. Notably, blocking Prss29 activity was sufficient to rescue subfertility in Wt1ko/+ female mice indicating Prss29 as a critical factor in female fertility. Furthermore, we have identified a missense mutation in a patient with idiopathic infertility leading to an amino acid exchange within the zinc finger domain of WT1 and resulting in reduced DNA binding. We demonstrate that Wt1 represses expression of Prss29 and that its de-repression and precocious expression in the oviduct interferes with pre-implantation development. Our study reveals a novel role for Wt1 in early mammalian development and identifies proteases as critical mediators of the maternal-embryonic crosstalk. We believe that our data regarding the importance of a proteostatic environment in the oviduct are also relevant for female fertility in humans. We anticipate that our findings will form the basis for the identification of further causes of idiopathic infertility. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:27:01.534.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hendrik Nolte |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-12-07 00:40:09 | ID requested | |
1 | 2017-04-04 02:19:37 | announced | |
⏵ 2 | 2024-10-22 04:27:02 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1093/hmg/ddx075; |
Nathan A, Reinhardt P, Kruspe D, J, ö, r, ß T, Groth M, Nolte H, Habenicht A, Herrmann J, Holschbach V, Toth B, Kr, ü, ger M, Wang ZQ, Platzer M, Englert C, The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis. Hum Mol Genet, 26(9):1694-1705(2017) [pubmed] |
Keyword List
curator keyword: Biological, Biomedical |
submitter keyword: Oviductal fluid, Wt1, LC-MS/MS, Prss29 |
Contact List
Marcus Krueger |
contact affiliation | Institute for Genetics and CECAD, University of Cologne, 50931 Cologne, Germany |
contact email | marcus.krueger@uni-koeln.de |
lab head | |
Hendrik Nolte |
contact affiliation | Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) |
contact email | h.nolte@uni-koeln.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD003283
- Label: PRIDE project
- Name: Oviductal fluid LC-MS/MS - The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis