2型糖尿病(T2DM)是男性不育的危险因素,但潜在的分子机制仍不清楚。晚期糖基化终末产物(AGEs)是糖尿病血管并发症的致病分子。这里,我们在T2DM小鼠模型中研究了抗AGEs的DNA适体(AGE-Apt)对睾丸和精子异常的影响.处死KK-Ay(DM)和野生型(非DM)4周龄和7周龄雄性小鼠,收集睾丸和精子进行免疫荧光,RT-PCR,和组织学分析。将7周龄的DM和非DM小鼠皮下输注AGE-Apt或对照适体6周,然后处死。血浆葡萄糖,睾丸AGEs,以及4周龄DM小鼠的Rage基因表达和血浆葡萄糖,睾丸AGEs,氧化应激,7周龄DM小鼠促炎基因表达高于同龄非DM小鼠,后者与生精管扩张有关。AGE-Apt不影响血糖参数,但它能抑制生精管扩张,减少睾丸巨噬细胞和凋亡细胞的数量,恢复了精子浓度的下降,运动性,和13周龄DM小鼠的生存力。我们的发现表明,AGEs-Apt可能通过抑制AGE诱导的DM小鼠睾丸氧化应激和炎症来改善精子异常。
Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (
AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against
AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular
AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular
AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that
AGEs-Apt may improve sperm abnormality by suppressing AGE-RAGE-induced oxidative stress and inflammation in the testes of DM mice.