Magee Womens Research Institute, Pittsburgh, Pennsylvania, USA; Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India.
J Diabetes. 2014 Jan;6(1):48-59. doi: 10.1111/1753-0407.12068. Epub 2013 Jul 23.
There has been a marked increase in the prevalence of childhood and/or adolescent diabetes worldwide. Testicular dysfunction in adult-onset diabetes is well established, whereas the impact of early onset diabetes on the functional development of the testis remains elusive. In the present study we investigated early oxidative impairments and progressive histological changes in streptozotocin (STZ)-induced diabetic prepubertal rat testis.
Testes were sampled from prepubertal rats injected with a single bolus of STZ (90 mg/kg, i.p.) on Days 1, 3, 5, 7 and 14 after STZ injection for quantitation of testicular oxidative stress parameters in isolated subcellular fractions and mitochondrial and microsomal functional efficiency, as well as at weekly intervals over a period of 8 weeks for histological and flow cytometry analyses.
Prepubertal diabetic rats were severely hyperglycemic with reduced testes size. At the subcellular level, a progressive increase in oxidative stress parameters was discernible in the cytosolic and microsomal compartments from Day 1 after STZ, together with decreased antioxidant defenses. Surprisingly, tissue ascorbate and free catalytic iron levels were notably increased in diabetic rat testis. Mitochondrial dysfunction was manifested from Day 5, as evidenced by a reduction in electron transport activity. Histologically, tissue sections showed distorted seminiferous tubules and extensive cell vacuolization with progressive disappearance of spermatids in the lumen by Week 7 after STZ injection, observations that were consistent with flow cytometry data.
Herein we provide evidence that the onset of diabetes brings about oxidative changes at the subcellular level that cumulatively affect the functional growth of testes.
全球范围内儿童和/或青少年糖尿病的患病率显著增加。成年发病型糖尿病的睾丸功能障碍已得到证实,而早期发病型糖尿病对睾丸功能发育的影响仍不清楚。在本研究中,我们研究了链脲佐菌素(STZ)诱导的青春期前糖尿病大鼠睾丸早期氧化损伤和进行性组织学变化。
在 STZ 注射后第 1、3、5、7 和 14 天,通过单次腹腔注射 STZ(90mg/kg),从小鼠睾丸中取样,以定量测定分离的亚细胞成分中的睾丸氧化应激参数和线粒体及微粒体功能效率,以及在 8 周的时间内每周进行一次组织学和流式细胞术分析。
青春期前糖尿病大鼠血糖严重升高,睾丸体积缩小。在亚细胞水平,从 STZ 后第 1 天开始,细胞质和微粒体部分的氧化应激参数逐渐增加,同时抗氧化防御能力下降。令人惊讶的是,糖尿病大鼠睾丸组织中的抗坏血酸和游离催化铁水平明显增加。从第 5 天开始出现线粒体功能障碍,表现为电子传递活性降低。组织切片显示,曲细精管扭曲,细胞空泡化广泛,腔内精子细胞逐渐消失,这些观察结果与流式细胞术数据一致。
本文提供的证据表明,糖尿病的发生会导致亚细胞水平的氧化变化,这些变化会累积影响睾丸的功能生长。