title: Advanced glycation end products accumulate in the reproductive tract of men with diabetes.
abstract: Light microscopic studies comparing sperm parameters show little association between diabetes and male fertility. However, with the introduction of new analytical techniques, evidence is now emerging of previously undetectable effects of diabetes on sperm function. Specifically, a recent study has found a significantly higher sperm nuclear DNA fragmentation in diabetic men. As advanced glycation end products (AGEs) are important instigators of oxidative stress and cell dysfunction in numerous diabetic complications, we hypothesized that these compounds could also be present in the male reproductive tract. The presence and localization of the most prominent AGE, carboxymethyl-lysine (CML), in the human testis, epididymis and sperm was determined by immunohistochemistry. Parallel ELISA and Western blot analyses were performed to ascertain the amount of CML in seminal plasma and sperm from 13 diabetic and nine non-diabetic subjects. CML immunoreactivity was found throughout the seminiferous epithelium, the nuclei of spermatogonia and spermatocytes, in the basal and principle cells cytoplasm and nuclei of the caput epididymis and on most sperm tails, mid pieces and all cytoplasmic droplets. The acrosomal cap, especially the equatorial band, was prominently stained in diabetic samples only. The amount of CML was significantly higher (p = 0.004) in sperm from non-diabetic men. Considering the known detrimental actions of AGEs in other organs, the presence, location and quantity of CML, particularly the increased expression found in diabetic men, suggest that these compounds may play a hitherto unrecognized role in male infertility.
authors.affiliation: Obstetrics and Gynecology, School of Medicine, Queen's University of Belfast, Belfast, UK. c.mallidis@qub.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Mallidis
authors.forename: I M
authors.initials: IM
authors.lastname: Agbaje
authors.forename: D A
authors.initials: DA
authors.lastname: Rogers
authors.forename: J V
authors.initials: JV
authors.lastname: Glenn
authors.forename: R
authors.initials: R
authors.lastname: Pringle
authors.forename: A B
authors.initials: AB
authors.lastname: Atkinson
authors.forename: K
authors.initials: K
authors.lastname: Steger
authors.forename: A W
authors.initials: AW
authors.lastname: Stitt
authors.forename: N
authors.initials: N
authors.lastname: McClure
mesh_terms: D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004822:Epididymis / Q000737:chemistry*; D017127:Glycation End Products, Advanced / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000209:etiology / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D008297:Male; D012661:Semen / Q000737:chemistry*; D013094:Spermatozoa / Q000737:chemistry*; D013737:Testis / Q000737:chemistry*
chemical_list: D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D008239:Lysine