Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy

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Howell, Matthew
Singh, Natalia
Seo, Joonbae
Whitley, Elizabeth
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Singh, Ravindra
Ottesen, Eric
Research Scientist II
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Biomedical Sciences

The Department of Biomedical Sciences aims to provide knowledge of anatomy and physiology in order to understand the mechanisms and treatment of animal diseases. Additionally, it seeks to teach the understanding of drug-action for rational drug-therapy, as well as toxicology, pharmacodynamics, and clinical drug administration.

The Department of Biomedical Sciences was formed in 1999 as a merger of the Department of Veterinary Anatomy and the Department of Veterinary Physiology and Pharmacology.

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  • College of Veterinary Medicine (parent college)
  • Department of Veterinary Anatomy (predecessor, 1997)
  • Department of Veterinary Physiology and Pharmacology (predecessor, 1997)

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Veterinary Pathology
The Department of Veterinary Pathology Labs provides high quality diagnostic service to veterinarians in Iowa and throughout the Midwest. Packages may be delivered through the postage service or by dropping samples off at our lab in Iowa State University’s College of Veterinary Medicine campus.
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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.


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

Fri Jan 01 00:00:00 UTC 2016