Testosterone deficiency accompanied by testicular and epididymal abnormalities in TMF(-/-) mice

Mol Cell Endocrinol. 2013 Jan 5;365(1):52-63. doi: 10.1016/j.mce.2012.09.003. Epub 2012 Sep 20.


TMF/ARA160 is a Golgi-associated protein, which is essential for spermiogenesis. In this study, we show that lack of TMF/ARA160 leads to defects in both the testis and the epididymis. In the testis, spermatid retention and extensive proliferation of Leydig cells were observed. Concomitantly, the serum levels of luteinizing hormone (LH), a stimulator of Leydig cell proliferation, were significantly increased in TMF(-/-) mice. Structural and functional defects were also seen in the epididymis. These included apoptosis of epithelial epididymal cells and sperm stasis in the cauda. Notably, the serum testosterone levels of TMF(-/-) mice were significantly lower than those of wt mice, and external testosterone administration decreased the number of apoptotic epithelial epididymal cells in TMF(-/-) animals. In summary, we show here for the first time that TMF/ARA160 participates in the control of serum testosterone levels in males, and its absence results in major testicular and epididymal defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Apoptosis
  • Cell Proliferation
  • DNA-Binding Proteins
  • Epididymis / abnormalities
  • Epididymis / metabolism
  • Epididymis / pathology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Golgi Matrix Proteins
  • Hormone Replacement Therapy
  • Leydig Cells / enzymology
  • Leydig Cells / metabolism
  • Leydig Cells / pathology
  • Luteinizing Hormone / blood
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Spermatogenesis
  • Testis / abnormalities
  • Testis / metabolism
  • Testis / pathology*
  • Testosterone / blood*
  • Testosterone / metabolism
  • Testosterone / therapeutic use
  • Transcription Factors
  • Ubiquitin-Protein Ligases / deficiency
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Vesicular Transport Proteins / deficiency
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • DNA-Binding Proteins
  • Golgi Matrix Proteins
  • RNA, Messenger
  • Tmf1 protein, mouse
  • Transcription Factors
  • Vesicular Transport Proteins
  • Testosterone
  • Luteinizing Hormone
  • Ubiquitin-Protein Ligases