Chromatin remodelling in spermatids is an essential step in spermiogenesis and involves the exchange of most histones by protamines, which drives chromatin condensation in late spermatids. The gene Rimklb encodes a citrylglutamate synthase highly expressed in testes of vertebrates and the increase of its reaction product, β-citrylglutamate, correlates in time with the appearance of spermatids. Here we show that deficiency in a functional Rimklb gene leads to male subfertility, which could be partially rescued by in vitro fertilization. Rimklb-deficient mice are impaired in a late step of spermiogenesis and produce spermatozoa with abnormally shaped heads and nuclei. Sperm chromatin in Rimklb-deficient mice was less condensed and showed impaired histone to protamine exchange and retained transition protein 2. These observations suggest that citrylglutamate synthase, probably via its reaction product β-citrylglutamate, is essential for efficient chromatin remodelling during spermiogenesis and may be a possible candidate gene for male subfertility or infertility in humans.
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May 2022
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Cover Image
Cover Image
Immunofluorescence staining of TP1 in seminiferous tubules from RimklbIII +/+ and Rim k lb/mice. Nuclei were stained with DAPI and the acrosome with PNA lectin. TP1 was present in seminiferous stages II in both genotypes. TP1 was undetectable at stage VII bars, 50 µm. Image from Eckhardt and colleagues (pp. 953–972).
Research Article|
May 06 2022
Citrylglutamate synthase deficient male mice are subfertile with impaired histone and transition protein 2 removal in late spermatids
Lihua Wang-Eckhardt;
Lihua Wang-Eckhardt
Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing - review & editing
1Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany
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Marc Sylvester;
Marc Sylvester
Resources, Data curation, Formal analysis, Investigation, Methodology, Writing - review & editing
2Core Facility Mass Spectrometry, Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany
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Ivonne Becker;
Ivonne Becker
Investigation, Visualization, Writing - review & editing
1Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany
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Jean-Pierre Allam;
Jean-Pierre Allam
Conceptualization, Writing - review & editing
3Department of Dermatology and Allergy, Medical Faculty, University of Bonn, Bonn, Germany
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Matthias Eckhardt
Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing
1Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, Germany
Correspondence: Matthias Eckhardt (eckhardt@uni-bonn.de)
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Publisher: Portland Press Ltd
Received:
December 15 2021
Revision Received:
April 13 2022
Accepted:
April 14 2022
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem J (2022) 479 (9): 953–972.
Article history
Received:
December 15 2021
Revision Received:
April 13 2022
Accepted:
April 14 2022
Citation
Lihua Wang-Eckhardt, Marc Sylvester, Ivonne Becker, Jean-Pierre Allam, Matthias Eckhardt; Citrylglutamate synthase deficient male mice are subfertile with impaired histone and transition protein 2 removal in late spermatids. Biochem J 13 May 2022; 479 (9): 953–972. doi: https://doi.org/10.1042/BCJ20210844
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