Distribution of the receptor for advanced glycation end products in the human male reproductive tract: prevalence in men with diabetes mellitus.
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.
Mallidis
Con
C
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
Agbaje
Ishola
I
Rogers
Deirdre
D
Glenn
Josephine
J
McCullough
Stephen
S
Atkinson
A Brew
AB
Steger
Klaus
K
Stitt
Alan
A
McClure
Neil
N
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*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic