Experimental diabetes-induced testicular damage in prepubertal rats (在青春期前大鼠中实验性糖尿病导致的睾丸损伤)

Background 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. Methods 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. Results 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. Conclusions 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. 摘要 背景 全世界儿童期和/或青春期糖尿病的患病率在显著增加。在成年发病的糖尿病中睾丸功能障碍已经很明确了，然而早期发病的糖尿病对睾丸功能发育的影响目前尚未明确。在本研究中，我们调查了链脲霉素（STZ）诱导的青春期前糖尿病大鼠睾丸中的早期氧化损伤以及逐渐进展的组织学变化情况。 方法 青春期前大鼠注射一次单剂量的STZ（90 mg/kg，腹膜内注射），在注射STZ后的第1、3、5、7与14日分别从它们的睾丸取样，在分离的亚细胞片段中定量测量睾丸的氧化应激指标以及线粒体与微粒体的功能效率，除此之外，每周一次进行组织学与流式细胞仪的分析，共8周。 结果 青春期前糖尿病大鼠出现了严重高血糖，同时睾丸体积也缩小了。从注射STZ后第1日开始，在亚细胞水平可以清楚地观察到胞浆与微粒体中的氧化应激指标进行性增加，与此同时抗氧化的防御系统在不断地减弱。令人惊讶的是，在糖尿病大鼠的睾丸中，组织抗坏血酸以及游离催化铁的水平也有显著的增加。从第5日开始出现线粒体功能障碍，其证据就是电子传递活动减少。到了注射STZ后的第7周，在组织学上，组织切片显示曲细精管扭曲以及广泛的细胞空泡化，同时管腔内的精子细胞进展性消失，这些观测结果与流式细胞仪数据相一致。 结论 我们证实了发生糖尿病后可导致亚细胞水平的氧化变化，累积后可影响睾丸功能的发育。