title: Distribution of the receptor for advanced glycation end products in the human male reproductive tract: prevalence in men with diabetes mellitus.
abstract: BACKGROUND
  Diabetics have a significantly higher percentage of sperm with nuclear DNA (nDNA) fragmentation and increased levels of advanced glycation end products (AGEs), in their testis, epididymis and sperm. As the receptor for AGEs (RAGE) is important to oxidative stress and cell dysfunction, we hypothesise, that it may be involved in sperm nDNA damage.
  
  
  METHODS
  Immunohistochemistry was performed to determine the presence of RAGE in the human testis and epididymis. A comparison of the receptor's incidence and localization on sperm from 10 diabetic and 11 non-diabetic men was conducted by blind semi-quantitative assessment of the immunostaining. Enzyme-linked immunosorbent assay analysis ascertained RAGE levels in seminal plasma and sperm from 21 diabetic and 31 non-diabetic subjects. Dual labelling immunolocalization was employed to evaluate RAGE's precise location on the sperm head.
  
  
  RESULTS
  RAGE was found throughout the testis, caput epididymis, particularly the principle cells apical region, and on sperm acrosomes. The number of sperm displaying RAGE and the overall protein amount found in sperm and seminal plasma were significantly higher in samples from diabetic men (P < 0.01, P < 0.0001 and P < 0.0001, respectively).
  
  
  CONCLUSIONS
  The presence of RAGE implies that it may play a central role in sperm nDNA damage particularly in diabetic men where the levels are elevated.
authors.affiliation: Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, School of Medicine, Queen's University of Belfast, Grosvenor Road, Belfast, UK. c.mallidis@qub.ac.uk
authors.forename: Con
authors.initials: C
authors.lastname: Mallidis
authors.forename: Ishola
authors.initials: I
authors.lastname: Agbaje
authors.forename: Deirdre
authors.initials: D
authors.lastname: Rogers
authors.forename: Josephine
authors.initials: J
authors.lastname: Glenn
authors.forename: Stephen
authors.initials: S
authors.lastname: McCullough
authors.forename: A Brew
authors.initials: AB
authors.lastname: Atkinson
authors.forename: Klaus
authors.initials: K
authors.lastname: Steger
authors.forename: Alan
authors.initials: A
authors.lastname: Stitt
authors.forename: Neil
authors.initials: N
authors.lastname: McClure
mesh_terms: D000293:Adolescent; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004822:Epididymis / Q000737:chemistry*; D017127:Glycation End Products, Advanced; D006801:Humans; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis*; D012661:Semen / Q000737:chemistry*; D013737:Testis / Q000737:chemistry*
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic