Erkilinc G, Ozdamar G, Ozmen O, Yüceer R O
Department of Medical Pathology, İzmir Bakircay University, İzmir, Turkey.
Faculty of Medicine, Department of Psychiatry, Suleyman Demirel University, Isparta, Turkey.
Biotech Histochem. 2025 Feb;100(2):41-49. doi: 10.1080/10520295.2024.2448489. Epub 2025 Jan 15.
The main symptoms of depression, a chronic mental illness, include sadness, low self-esteem, and a diminished sense of enjoyment in life. Many factors have been suggested to be associated with depression, one of which is low testosterone in men. The serotonin reuptake inhibitor fluoxetine (FLU), used to treat depression, has been reported to potentially have detrimental effects on spermatogenesis in rats after long-term use. The multimodal antidepressant vortioxetine (VTX) offers new promise for the treatment of depression. The chronic unpredictable mild stress (CUMS) model is widely known as an experimental paradigm used to study depression-like behaviors in rodents. Stress leads to various neurochemical and immune changes, affecting multiple organs. Our study aims to examine the histopathological findings in testicular tissue induced by CUMS and the immunohistochemical expression of Cas-8, IL-6, and RANKL using a depression model in rats. Rats were split into 4 groups of 7 animals each at random. Group 1 (control) did not experience any stress. Group 2 (CUMS) was exposed to chronic, unpredictable mild stress using a specific procedure. Group 3 (CUMS+VTX) and Group 4 (CUMS+FLU) underwent CUMS and received intraperitoneal drug treatment at a dose of 10 mg/kg during the final three weeks of the study. The rat testicles collected during necropsy were evaluated histopathologically and immunohistochemically for Cas-8, IL-6, and RANKL expressions using a light microscope. In Group 1, histological analysis showed normal tissue architecture in the testicles and epididymis. In Group 2, there was significant depletion of spermatozoa in the seminiferous tubules and empty tubules in the epididymis. In Groups 3 and 4, FLU and VTX treatment led to improvements in the testicles. Cas-8, RANKL, and IL-6 immunohistochemistry revealed increased expression in Group 2, primarily in interstitial cells. In Groups 1, 3, and 4, no or very slight expression of these markers was observed. The results of this study showed that sperm production in the testes is negatively affected in CUMS-induced depression and that Cas-8, IL-6, and RANKL expression is increased, particularly in interstitial cells. VTX and FLU, used in the treatment of depression, suggest potential for mitigating the adverse effects of CUMS on the testes.
抑郁症是一种慢性精神疾病，其主要症状包括悲伤、自卑以及生活乐趣感降低。许多因素被认为与抑郁症有关，其中之一是男性体内睾酮水平低。用于治疗抑郁症的血清素再摄取抑制剂氟西汀（FLU），据报道长期使用后可能对大鼠的精子发生有不利影响。多模式抗抑郁药伏硫西汀（VTX）为抑郁症治疗带来了新希望。慢性不可预测轻度应激（CUMS）模型是一种广泛用于研究啮齿动物抑郁样行为的实验范式。应激会导致各种神经化学和免疫变化，影响多个器官。我们的研究旨在使用大鼠抑郁症模型检查CUMS诱导的睾丸组织的组织病理学发现以及胱天蛋白酶-8（Cas-8）、白细胞介素-6（IL-6）和核因子κB受体活化因子配体（RANKL）的免疫组化表达。将大鼠随机分为4组，每组7只动物。第1组（对照组）未经历任何应激。第2组（CUMS组）采用特定程序暴露于慢性、不可预测的轻度应激。第3组（CUMS+VTX组）和第4组（CUMS+FLU组）接受CUMS处理，并在研究的最后三周接受腹腔内药物治疗，剂量为10mg/kg。在尸检时收集的大鼠睾丸进行组织病理学评估，并使用光学显微镜对Cas-8、IL-6和RANKL表达进行免疫组化评估。在第1组中，组织学分析显示睾丸和附睾的组织结构正常。在第2组中，生精小管中的精子明显减少，附睾中的小管空虚。在第3组和第4组中，FLU和VTX治疗使睾丸情况有所改善。Cas-8、RANKL和IL-6免疫组化显示第2组表达增加，主要在间质细胞中。在第1组、第3组和第4组中，未观察到这些标志物的表达或表达非常轻微。本研究结果表明，CUMS诱导的抑郁症会对睾丸中的精子生成产生负面影响，并且Cas-8、IL-6和RANKL表达增加，尤其是在间质细胞中。用于治疗抑郁症的VTX和FLU表明有可能减轻CUMS对睾丸的不良影响。
