Embryonic lethality and defective male germ cell development in mice lacking UTF1

Seth D Kasowitz,P Jeremy Wang,N Adrian Leu,Jun Ma,Mengcheng Luo

doi:10.1038/s41598-017-17482-z

Seth D Kasowitz, P Jeremy Wang + Show 3 more

Open Access

https://doi.org/10.1038/s41598-017-17482-z

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Journal: Scientific Reports	Publication Date: Dec 1, 2017
Citations: 10	License type: open-access

Affiliation: University of Pennsylvania

Abstract

The germ cell lineage is specified early in embryogenesis and undergoes complex developmental programs to generate gametes. Here, we conducted genetic studies to investigate the role of Utf1 (Undifferentiated embryonic cell transcription factor 1) in mouse germ cell development. Utf1 is expressed in pluripotent embryonic stem (ES) cells and regulates ES cell differentiation. In a proteomics screen, we identified UTF1 among 38 proteins including DNMT3L and DND1 that associate with chromatin in embryonic testes. We find that UTF1 is expressed in embryonic and newborn gonocytes and in a subset of early spermatogonia. Ubiquitous inactivation of Utf1 causes embryonic lethality in mice with a hybrid genetic background. Male mice with a germline-specific deletion of Utf1 resulting from Prdm1-Cre mediated recombination are born with significantly fewer gonocytes and exhibit defective spermatogenesis and reduced sperm count as young adults. These defects are ameliorated in older animals. These results demonstrate that UTF1 is required for embryonic development and regulates male germ cell development.

Highlights

In sexually reproducing organisms, germ cells pass genetic information to the generation
UTF1 modulates the epigenetic state of bivalent genes and prevents aberrant gene expression through mRNA decapping in Embryonic stem (ES) cells[7,10]
We report that UTF1 plays important roles during two stages of mouse male germ cell development: embryonic gonocyte development and postnatal spermatogenesis

Summary

Introduction

Germ cells pass genetic information to the generation. UTF1 modulates the epigenetic state of bivalent genes and prevents aberrant gene expression through mRNA decapping in ES cells[7,10]. These UTF1 functions are critical for ES cell pluripotency and differentiation. Utf[1] is expressed in the inner cell mass, the primitive ectoderm and the extra-embryonic tissue, but not in the mesoderm[5]. We identified UTF1 as one of 38 chromatin-associated proteins enriched in developing male embryonic germ cells. Inactivation of Utf[1] leads to a reduction in the number of gonocytes at birth and defective spermatogenesis in adult males

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