Mallidis C, Agbaje I M, Rogers D A, Glenn J V, Pringle R, Atkinson A B, Steger K, Stitt A W, McClure N
Obstetrics and Gynecology, School of Medicine, Queen's University of Belfast, Belfast, UK.
Int J Androl. 2009 Aug;32(4):295-305. doi: 10.1111/j.1365-2605.2007.00849.x. Epub 2008 Jan 22.
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.
比较精子参数的光学显微镜研究表明，糖尿病与男性生育能力之间几乎没有关联。然而，随着新分析技术的引入，现在有证据表明糖尿病对精子功能存在以前未被检测到的影响。具体而言，最近一项研究发现糖尿病男性的精子核DNA碎片化程度明显更高。由于晚期糖基化终产物（AGEs）是许多糖尿病并发症中氧化应激和细胞功能障碍的重要诱因，我们推测这些化合物也可能存在于男性生殖道中。通过免疫组织化学确定了最主要的AGE——羧甲基赖氨酸（CML）在人类睾丸、附睾和精子中的存在及定位。对13名糖尿病患者和9名非糖尿病患者的精液和精子进行了平行酶联免疫吸附测定（ELISA）和蛋白质免疫印迹分析，以确定CML的含量。在整个生精上皮、精原细胞和精母细胞的细胞核、附睾头的基底细胞和主细胞的细胞质及细胞核以及大多数精子的尾部、中段和所有细胞质滴中均发现了CML免疫反应性。仅在糖尿病样本中，顶体帽，尤其是赤道带，被显著染色。非糖尿病男性精子中的CML含量显著更高（p = 0.004）。考虑到AGEs在其他器官中已知的有害作用，CML的存在、位置和数量，特别是在糖尿病男性中发现的表达增加，表明这些化合物可能在男性不育中发挥了迄今未被认识到的作用。
