Dataset Information

Oviductal fluid LC-MS/MS - The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Oviductal Fluid

SUBMITTER: Hendrik Nolte

LAB HEAD: Marcus Krueger

PROVIDER: PXD003283 | Pride | 2017-04-04

REPOSITORIES: Pride

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			Action	DRS
	20131206_HN__AbinazaNathan_InGel_1974_01_131206095536.raw	Raw
	20131206_HN__AbinazaNathan_InGel_1974_02.raw	Raw
	20131206_HN__AbinazaNathan_InGel_1974_03.raw	Raw
	20131206_HN__AbinazaNathan_InGel_1974_04.raw	Raw
	20131206_HN__AbinazaNathan_InGel_1974_05.raw	Raw

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The Wilms tumor protein Wt1 contributes to female fertility by regulating oviductal proteostasis.

Nathan Abinaya A Reinhardt Peter P Kruspe Dagmar D Jörß Tjard T Groth Marco M Nolte Hendrik H Habenicht Andreas A Herrmann Jörg J Holschbach Verena V Toth Bettina B Krüger Marcus M Wang Zhao-Qi ZQ Platzer Matthias M Englert Christoph C

Human molecular genetics 20170501 9

Although the zinc finger transcription factor Wt1 has been linked to female fertility, its precise role in this process has not yet been understood. We have sequenced the WT1 exons in a panel of patients with idiopathic infertility and have identified a missense mutation in WT1 in one patient out of eight. This mutation leads to an amino acid change within the zinc finger domain and results in reduced DNA binding. We utilized Wt1+/- mice as a model to mechanistically pinpoint the consequences of ...[more]

PMID: 28334862

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