Solek Przemyslaw, Mytych Jennifer, Sujkowska Ewelina, Grzegorczyk Magdalena, Jasiewicz Patrycja, Sowa-Kucma Magdalena, Stachowicz Katarzyna, Koziorowski Marek, Tabecka-Lonczynska Anna
Department of Biotechnology, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow, Pigonia 1, 35-310 Rzeszów, Poland.
Department of Human Physiology, Institute of Medical Sciences, Medical College of Rzeszow University, Kopisto 2a, 35-959, Rzeszow, Poland.
Toxicol Res. 2021 May 20;38(2):175-186. doi: 10.1007/s43188-021-00098-x. eCollection 2022 Apr.
The increasing number of depression cases leads to a greater need for new antidepressant treatment development. It is postulated that antidepressants may harm male fertility, but the cellular mechanism is still poorly understood. The role of growth factors and klotho protein in maintaining normal male reproductive function is well documented. Hence, the study aimed to investigate the effect of the antidepressant drug - imipramine (tricyclic AD), and other substances with antidepressant potential (ALS), administered in combination or in combination with LPS (an animal model of depression) on gene expression and protein synthesis of IGF-2 (insulin-like growth factor 2), TGF-β1 (transforming growth factor β1), NGF (nerve growth factor), KGF (keratinocyte growth factor) and protein synthesis of VEGF-A (vascular endothelial growth factor A), IGF-IR (insulin-like growth factor receptor 1), EGFR (epidermal growth factor receptor) and klotho in the testis of mice. Mice were injected intraperitoneally with selected ALS and LPS or 10% DMSO (controls) (n = 7/group) once a day for 14 days. Animals were decapitated and testes collected for RNA and protein purification. PCR and western blot methods were employed for the evaluation of growth factors and klotho expression. The results obtained indicated a decreased level of most of the analyzed genes and proteins, except KGF; its expression increased after treatment with MTEP and IMI administrated individually and after NS-398, and IMI in combination with LPS. Our results may suggest that the tested ALS and LPS can contribute to a reduction of male fertility, but NS-398, IMI, and IMI+NS-398 may also act as stimulants after LPS.
抑郁症病例数量的不断增加导致对新型抗抑郁药物研发的需求日益增长。据推测，抗抑郁药可能会损害男性生育能力，但其细胞机制仍知之甚少。生长因子和klotho蛋白在维持正常男性生殖功能中的作用已有充分记录。因此，本研究旨在探讨抗抑郁药物丙咪嗪（三环类抗抑郁药）以及其他具有抗抑郁潜力的物质（ALS）单独使用或与脂多糖（一种抑郁症动物模型）联合使用对小鼠睾丸中胰岛素样生长因子2（IGF-2）、转化生长因子β1（TGF-β1）、神经生长因子（NGF）、角质形成细胞生长因子（KGF）的基因表达和蛋白合成以及血管内皮生长因子A（VEGF-A）、胰岛素样生长因子受体1（IGF-IR）、表皮生长因子受体（EGFR）和klotho蛋白合成的影响。小鼠每天腹腔注射一次选定的ALS和脂多糖或10%二甲亚砜（对照组）（每组n = 7），持续14天。动物断头后收集睾丸用于RNA和蛋白质纯化。采用PCR和蛋白质印迹法评估生长因子和klotho的表达。所得结果表明，除KGF外，大多数分析的基因和蛋白质水平均降低；单独用MTEP和IMI处理后以及用NS-398和IMI联合脂多糖处理后，KGF的表达增加。我们的结果可能表明，所测试的ALS和脂多糖可能导致男性生育能力下降，但NS-398、IMI以及IMI + NS-398在脂多糖作用后也可能起到刺激作用。
