Deletion of NFIX results in defective progression through meiosis within the mouse testis†.


Journal

Biology of reproduction
ISSN: 1529-7268
Titre abrégé: Biol Reprod
Pays: United States
ID NLM: 0207224

Informations de publication

Date de publication:
13 06 2022
Historique:
received: 20 11 2022
revised: 17 01 2022
accepted: 24 02 2022
pubmed: 5 3 2022
medline: 18 6 2022
entrez: 4 3 2022
Statut: ppublish

Résumé

Members of the nuclear factor I (NFI) family are key regulators of stem cell biology during development, with well-documented roles for NFIA, NFIB, and NFIX in a variety of developing tissues, including brain, muscle, and lung. Given the central role these factors play in stem cell biology, we posited that they may be pivotal for spermatogonial stem cells or further developing spermatogonia during testicular development. Surprisingly, in stark contrast to other developing organ systems where NFI members are co-expressed, these NFI family members show discrete patterns of expression within the seminiferous tubules. Sertoli cells (spermatogenic supporting cells) express NFIA, spermatocytes express NFIX, round spermatids express NFIB, and peritubular myoid cells express each of these three family members. Further analysis of NFIX expression during the cycle of the seminiferous epithelium revealed expression not in spermatogonia, as we anticipated, but in spermatocytes. These data suggested a potential role for NFIX in spermatogenesis. To investigate, we analyzed mice with constitutive deletion of Nfix (Nfix-null). Assessment of germ cells in the postnatal day 20 (P20) testes of Nfix-null mice revealed that spermatocytes initiate meiosis, but zygotene stage spermatocytes display structural defects in the synaptonemal complex, and increased instances of unrepaired DNA double-strand breaks. Many developing spermatocytes in the Nfix-null testis exhibited multinucleation. As a result of these defects, spermatogenesis is blocked at early diplotene and very few round spermatids are produced. Collectively, these novel data establish the global requirement for NFIX in correct meiotic progression during the first wave of spermatogenesis.

Identifiants

pubmed: 35243487
pii: 6541766
doi: 10.1093/biolre/ioac049
pmc: PMC9198952
doi:

Substances chimiques

NFI Transcription Factors 0
Nfix protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1191-1205

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM117155
Pays : United States

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Raul Ayala Davila (RA)

School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.

Cassy Spiller (C)

School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.

Danyon Harkins (D)

School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.

Tracey Harvey (T)

School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.

Philip W Jordan (PW)

Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Richard M Gronostajski (RM)

Department of Biochemistry, Program in Genetics, Genomics and Bioinformatics, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY, USA.

Michael Piper (M)

School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
Queensland Brain Institute, The University of Queensland, Brisbane, Australia.

Josephine Bowles (J)

School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.

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Classifications MeSH