Department of Biology, Faculty of Science, Istanbul University, Vezneciler, Istanbul, 34134, Turkey.
Department of Obstetrics and Gynecology, Perinatology Division, Antalya City Hospital, Antalya, Turkey.
Mol Biol Rep. 2024 Oct 10;51(1):1047. doi: 10.1007/s11033-024-09954-z.
Furan is an organic compound that occurs as a result of heat treatment during the processing and cooking of many food products. Furthermore, the environment contains furan in tobacco smoke and vehicle exhaust gases, and it serves as an intermediate molecule in the synthesis of various pharmaceutical and chemical agents, pesticides, and stabilizers. Studies on the male reproductive system have not been able to elucidate the pathway through which furan exerts its negative effects.
In this study, the TM3 Leydig cell line was exposed to various furan concentrations (0.03, 0.3, and 3 mM) for 24 h. In order to assess the cytotoxic effects of furan on Leydig cells, we examined cell viability, cell proliferation, and lactate dehydrogenase enzyme levels. To investigate the detrimental effects of furan on testosterone biosynthesis, quantitative analyses were conducted on cAMP and testosterone levels, as well as the expression levels of key genes and transcription factors implicated in the steroidogenic pathway. The results indicate that furan inhibited the viability and proliferation of Leydig cells and enhanced the activity of lactate dehydrogenase. Leydig cells administered to furan exhibited notable reductions in cAMP and testosterone levels. Additionally, while the expression levels of steroidogenic genes were downregulated, significant changes were detected in the expression levels of the transcription factors responsible for the regulation of these genes.
Consequently, our findings suggest that furan exerts inhibitory effects on steroidogenesis in Leydig cells through multiple mechanisms, ultimately leading to infertility by inducing dysfunction in Leydig cells.
呋喃是一种有机化合物，在许多食品的加工和烹饪过程中，由于热处理而产生。此外，环境中含有烟草烟雾和车辆废气中的呋喃，并且它作为各种药物和化学试剂、农药和稳定剂合成的中间分子。关于男性生殖系统的研究还未能阐明呋喃发挥其负面影响的途径。
在这项研究中，TM3 间质细胞系暴露于不同浓度的呋喃（0.03、0.3 和 3 mM）24 小时。为了评估呋喃对间质细胞的细胞毒性作用，我们检查了细胞活力、细胞增殖和乳酸脱氢酶酶水平。为了研究呋喃对睾丸激素生物合成的有害影响，对 cAMP 和睾丸激素水平以及参与甾体生成途径的关键基因和转录因子的表达水平进行了定量分析。结果表明，呋喃抑制间质细胞的活力和增殖，并增强乳酸脱氢酶的活性。给予呋喃的间质细胞 cAMP 和睾丸激素水平显著降低。此外，尽管甾体生成基因的表达水平下调，但负责调节这些基因的转录因子的表达水平发生了显著变化。
因此，我们的研究结果表明，呋喃通过多种机制对间质细胞的甾体生成产生抑制作用，最终通过诱导间质细胞功能障碍导致不育。
