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.

Identification of biochemical differences between different forms of male infertility by nuclear magnetic resonance (NMR) spectroscopy

“…Supporting the notion that diabetes effected changes in the metabolome of the testicle itself, the accumulation of advanced glycation end products accumulate in the reproductive tract of men with diabetes [25], and metabolic profile changes in the testes of mice with streptozotocin-induced type 1 diabetes mellitus has been reported [26].…”

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism

“…We identified high levels of N 3 -carboxymethyl-lysine (CML), the most prominent advanced glycation end product (AGE; Mallidis et al 2009) and its receptor (RAGE; Mallidis et al 2007) in the testis, epididymis and sperm of diabetic men and mouse models alike (O'Neill et al 2009). As this group of compounds is known to cause cellular dysfunction, oxidative stress and DNA damage in various organs and in a variety of conditions (Vlassara & Palace 2002), we hypothesise that they may also play an equally destructive role in the reproductive tract of diabetics and MetS patients and as such contribute to the sperm nDNA fragmentation seen in these men.…”

Infertile marriage in patients with diabetes mellitus

“…Было отмечено, что в биоптатах яичек мужчин с СД сни-жается количество клеток Лейдига по сравнению со здоро-выми мужчинами [7,8]. За трехлетний период клинического наблюдения за мужчинами с СД La Vignera S. с соавт.…”

“…Есть данные, что после субтотальной панкреатэктомии у мужчин развивалась атрофия придаточных половых желез (простаты, семенных пузырьков) [12]. У мужчин с СД в яичке, эпидиди-мисе и эякуляте была отмечена более высокая, по сравнению со здоровыми мужчинами, концентрация сложных конечных продуктов гликирования -показателей выраженности окси-дативного стресса [8]. Было показано, что в половой системе мужчин с СД, по сравнению со здоровыми мужчинами, повы-шено содержание прооксидантных веществ, равно как и сни-жена концентрация антиоксидантных субстанций [13,14].…”