Male reproductive dysfunction represents one of the overlooked consequences of diabetes that still deserve more scientific attention. We designed this study to explore the therapeutic potential of hydroxytyrosol (HT) on diabetic testicular damage and to investigate its relationship with adenosine monophosphate-activated protein kinase (AMPK) expression. In this context, 30 adult male Wistar rats were utilized and subdivided into control, diabetic and HT-treated diabetic groups. Testicular sections were prepared for histopathological examination and immunohistochemical detection of 8-hydroxy-2′-deoxyguanosine, Sertoli cell vimentin, myoid cell α-SMA, androgen receptors and caspase-3. We also assessed oxidative enzymatic and lipid peroxidation biochemical profiles, sperm count, morphology and motility. Real-time PCR of AMPK expression in tissue homogenate was performed. We observed that HT restored testicular histopathological structure and significantly reduced oxidative DNA damage and the apoptotic index. The HT-treated group also exhibited significantly higher Sertoli cell vimentin, myoid cell α-SMA and androgen receptor immune expression than the diabetic group. A rescue of the oxidative enzymatic activity, lipid peroxidation profiles, sperm count, morphology and motility to control levels was also evident in the HT-treated group. Significant upregulation of AMPK mRNA expression in the HT-treated group clarified the role of AMPK as an underlying molecular interface of the ameliorative effects of HT. We concluded that HT exhibited tangible antioxidant and antiapoptotic impacts on the testicular cytomorphological and immunohistochemical effects of experimentally induced diabetes. Furthermore, AMPK has an impactful role in the molecular machinery of these effects.

中文翻译：

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羟基酪醇对实验性糖尿病睾丸损伤的治疗前景：与 AMPK 表达的潜在相互作用

男性生殖功能障碍代表了糖尿病的一种被忽视的后果，仍然值得更多的科学关注。我们设计这项研究是为了探索羟基酪醇 (HT) 对糖尿病睾丸损伤的治疗潜力，并研究其与单磷酸腺苷活化蛋白激酶 (AMPK) 表达的关系。在这种情况下，使用了 30 只成年雄性 Wistar 大鼠并将其细分为对照组、糖尿病组和 HT 治疗的糖尿病组。制备睾丸切片用于8-羟基-2'-脱氧鸟苷、支持细胞波形蛋白、肌样细胞α-SMA、雄激素受体和caspase-3的组织病理学检查和免疫组化检测。我们还评估了氧化酶促和脂质过氧化生化特征、精子数量、形态和运动能力。对组织匀浆中的 AMPK 表达进行实时 PCR。我们观察到 HT 恢复了睾丸组织病理学结构并显着降低了氧化性 DNA 损伤和凋亡指数。HT 治疗组也表现出明显高于糖尿病组的支持细胞波形蛋白、肌样细胞 α-SMA 和雄激素受体免疫表达。在 HT 处理组中，氧化酶活性、脂质过氧化特征、精子数量、形态和运动力恢复到控制水平也很明显。HT 治疗组中 AMPK mRNA 表达的显着上调阐明了 AMPK 作为 HT 改善作用的潜在分子界面的作用。我们得出结论，HT 对实验诱导的糖尿病的睾丸细胞形态学和免疫组织化学作用表现出明显的抗氧化和抗细胞凋亡影响。此外，AMPK 在这些效应的分子机制中具有重要作用。