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Unpublished Paper
Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy
Scientific Reports
  • Eric W. Ottesen, Iowa State University
  • Matthew D Howell, Iowa State University
  • Natalia N. Singh, Iowa State University
  • Joonbae Seo, Iowa State University
  • Elizabeth M. Whitley, Iowa State University
  • Ravindra N. Singh, Iowa State University
Document Type
Article
Publication Version
Published Version
Publication Date
1-1-2016
DOI
10.1038/srep20193
Abstract
Spinal muscular atrophy (SMA) is caused by low levels of survival motor neuron (SMN), a multifunctional protein essential for higher eukaryotes. While SMN is one of the most scrutinized proteins associated with neurodegeneration, its gender-specific role in vertebrates remains unknown. We utilized a mild SMA model (C/C model) to examine the impact of low SMN on growth and development of mammalian sex organs. We show impaired testis development, degenerated seminiferous tubules, reduced sperm count and low fertility in C/C males, but no overt sex organ phenotype in C/C females. Underscoring an increased requirement for SMN expression, wild type testis showed extremely high levels of SMN protein compared to other tissues. Our results revealed severe perturbations in pathways critical to C/C male reproductive organ development and function, including steroid biosynthesis, apoptosis, and spermatogenesis. Consistent with enhanced apoptosis in seminiferous tubules of C/C testes, we recorded a drastic increase in cells with DNA fragmentation. SMN was expressed at high levels in adult C/C testis due to an adult-specific splicing switch, but could not compensate for low levels during early testicular development. Our findings uncover novel hallmarks of SMA disease progression and link SMN to general male infertility.
Comments

This article is from Scientific Reports 6 (2016): 20193, doi:10.1038/srep20193. Posted with permission.

Rights
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Copyright Owner
Ottesen, et al.
Language
en
File Format
application/pdf
Citation Information
Eric W. Ottesen, Matthew D Howell, Natalia N. Singh, Joonbae Seo, et al.. "Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy" Scientific Reports Vol. 6 (2016) p. 20193
Available at: http://works.bepress.com/ravindra-singh/20/