Lamas Celina A, Gollücke Andrea P B, Dolder Heidi
Department of Structural and Functional Biology, Biology Institute, State University of Campinas, Campinas, SP, Brazil.
Department of Biosciences, Federal University of Sao Paulo, Santos, SP, Brazil.
Int J Exp Pathol. 2015 Oct;96(5):301-10. doi: 10.1111/iep.12141. Epub 2015 Oct 30.
Cadmium is a well-known testicular toxicant, and parts of the world population are exposed chronically by inhalation or by food and water intake. Grape products have been highlighted as important sources of bioactive compounds, having anti-inflammatory, anti-oxidant and metal chelating properties. Since maintenance of tissue morphology is essential for testicular sperm development and hence male fertility, we analysed the protective effect of grape juice concentrate (GJC) (G8000(®) ) consumption on testicular morphology in rats exposed to cadmium. Thus, four groups of male Wistar rats (n = 6 per group), 50 days old, ingested either water or G8000(®) (2 g/kg/day) until they had completed one spermatogenic cycle in adult life (136 days old). Cadmium (1.2 mg / kg) was injected intraperitoneally when the animals were 80 days old into one of the water and one of the G8000 groups; intraperitoneal saline was used as a control in the other two groups. Animals anaesthetised and exsanguinated at 136 days and then perfused with Karnovsky's fixative and then the testes were collected for morphological analysis. We describe evident disruption of testicular morphology by cadmium, with alteration in tissue component proportions, reduced Leydig cells volume and initial signs of an inflammatory process. Ultrastructural analysis showed greater damage, suggesting spermatogenesis disruption. G8000(®) ingestion allowed tissue architecture to be re-established, as was corroborated by our stereological and morphometric findings. Animals from the group where G8000(®) had been administered together with cadmium revealed a significant reduction in macrophages and blood vessel volume, suggesting diminished inflammation, when compared to animals that received only cadmium. Moreover, smaller number of ultrastructural alterations was noted, revealing fewer areas of degeneration and disorganized interstitium. In conclusion, our results demonstrate that GJC consumption prevented the spermatogenic disruption promoted by cadmium, and thus could be a promising form of therapy against male infertility.
镉是一种广为人知的睾丸毒物，世界上部分人群通过吸入或经食物和水的摄入而长期接触镉。葡萄制品已被视为生物活性化合物的重要来源，具有抗炎、抗氧化和金属螯合特性。由于维持组织形态对于睾丸精子发育以及男性生育能力至关重要，我们分析了饮用浓缩葡萄汁（GJC）（G8000®）对镉暴露大鼠睾丸形态的保护作用。因此，将四组50日龄的雄性Wistar大鼠（每组n = 6），分别给予水或G8000®（2 g/kg/天），直至它们在成年期（136日龄）完成一个生精周期。当动物80日龄时，将镉（1.2 mg / kg）腹腔注射到其中一组饮用清水和一组饮用G8000的大鼠中；另外两组腹腔注射生理盐水作为对照。在136天时将动物麻醉、放血，然后用卡诺夫斯基固定液灌注，随后收集睾丸进行形态学分析。我们观察到镉明显破坏了睾丸形态，组织成分比例改变，睾丸间质细胞体积减小，并出现炎症过程的初始迹象。超微结构分析显示损伤更严重，提示生精过程受到破坏。饮用G8000®使组织结构得以重建，这得到了我们的体视学和形态测量学结果的证实。与仅接受镉处理的动物相比，同时给予G8000®和镉的组中的动物巨噬细胞和血管体积显著减少，提示炎症减轻。此外，超微结构改变的数量较少，退变区域和间质紊乱区域较少。总之，我们的结果表明，饮用GJC可防止镉导致的生精破坏，因此可能是一种有前景的治疗男性不育症的方法。
