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Oviductal expression data from wild type and Wt1 heterozygous mice

ABSTRACT: Comparison of gene expression in wild type and Wt1 (Wilms tumor suppressor gene 1) heterozygous knockout mice. Background: in Wt1+/- mice (MF1 strain) litter sizes are significantly smaller than in wild type animals. In addition, we observe retarded embryonic development of pre-implantation embryos that are still within the oviduct. By gene expression analysis we want to elucidate the molecular basis for these phenomena. 3 wild type and 3 heterozygous RNA samples

ORGANISM(S): Mus musculus

SUBMITTER: Abinaya Nathan

PROVIDER: E-GEOD-75924 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Oviductal expression data from wild type and Wt1 heterozygous mice

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Project 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.

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