PXD003283

PXD003283 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biological, Biomedical

submitter keyword: Oviductal fluid, Wt1, LC-MS/MS, Prss29

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/04/PXD003283

PRIDE project URI

• PRIDE
  1. PXD003283
     1. Label: PRIDE project
     2. Name: Oviductal fluid LC-MS/MS - The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis