title: Mouse germ cells go through typical epigenetic modifications after intratesticular tissue grafting.
abstract: BACKGROUND
  Since spermatogonial stem cell transplantation (SSCT) and testicular tissue grafting (TTG) may have important clinical applications, the safety of these promising techniques has to be proved. This study was designed to characterize epigenetic modifications in prepubertal and adult mouse germ cells and to study these epigenetic mechanisms after SSCT and TTG.
  
  
  METHODS
  Testicular cell suspensions were transplanted to the testes of genetically sterile W/W(v) recipients. Intratesticular tissue grafting was performed between green fluorescent protein (GFP(+)) donors and GFP(-) acceptor mice. DNMT1 and DNMT3A expression, the general methylation status and the histone modifications H3K4me3, H3K9ac, H4K5ac, H4K8ac, H4K12ac and H4K16ac were studied in a stage-dependent manner by immunohistochemistry and compared with data from adult control mice.
  
  
  RESULTS
  The expression levels of DNMT1 and DNMT3A, the DNA methylation status and most of the stage-specific histone modifications after SSCT or TTG were not different from fertile adult controls. Although, in elongated spermatids, the acetylation pattern was as expected, the stage-dependent expression of H4K5ac and H4K8ac was altered after SSCT.
  
  
  CONCLUSIONS
  Intratesticular tissue grafting might be the better choice for fertility restoration. Disrupting the stem cell niche might influence epigenetic patterns. Since the function of H4K5ac and H4K8ac in spermatogonia and spermatocytes still has to be explored, in-depth epigenetical analyses are warranted.
authors: Research Laboratory Biology of the Testis (BITE), Department of Embryology and Genetics, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels 1090, Belgium. ellen.goossens@uzbrussel.be
authors: E
authors: E
authors: Goossens
authors: T
authors: T
authors: Bilgec
authors: D
authors: D
authors: Van Saen
authors: H
authors: H
authors: Tournaye
mesh_terms: D000107:Acetylation; D000818:Animals; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008745:Methylation; D051379:Mice; D013093:Spermatogonia / Q000637:transplantation*; D013737:Testis / Q000637:transplantation*; D019737:Transplants
chemical_list: D006657:Histones