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Hum. Reprod. Advance Access originally published online on June 21, 2007
Human Reproduction 2007 22(8):2169-2177; doi:10.1093/humrep/dem156
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Distribution of the receptor for advanced glycation end products in the human male reproductive tract: prevalence in men with diabetes mellitus

Con Mallidis1,2,6, Ishola Agbaje1, Deirdre Rogers1, Josephine Glenn3, Stephen McCullough2, A. Brew Atkinson4, Klaus Steger5, Alan Stitt3 and Neil McClure1

1 Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, School of Medicine, Queen's University of Belfast, Grosvenor Road, Belfast BT12 6BJ UK 2 Division of Basic Medical Sciences/Anatomy, School of Medicine, Queen's University of Belfast, Belfast, UK 3 Centre for Vision Science and Vascular Biology, Queen's University of Belfast, Belfast, UK 4 Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, UK 5 Department of Urology and Paediatric Urology, Justus Liebig University, Giessen, Germany

6 Correspondence address. Tel: +44 28 90 63 2556; Fax: +44 28 90 32 8247; E-mail: c.mallidis{at}qub.ac.uk

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.

Key words: diabetes/epididymis/RAGE/sperm/testis

Submitted on February 23, 2007; resubmitted on April 19, 2007; accepted on April 28, 2007.


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