Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Islamic Republic of Iran.
Department of Clinical Biochemistry, Faculty of Veterinary Medicine, Tabriz, Islamic Republic of Iran.
Toxicology. 2024 May;504:153773. doi: 10.1016/j.tox.2024.153773. Epub 2024 Mar 12.
Aflatoxins (AFs) are inevitable environmental contaminants that are detrimental to human and animal health. AFs interfere with metabolic processes, metabolizing into different hydroxylated derivatives in the liver, as well as mechanistically induce ROS accumulation, S-phase arrest, DNA damage, and cell apoptosis. Chronic consumption of aflatoxin-contaminated foods can adversely affect the male reproductive system, cause testicular damage, prevent testosterone synthesis, decline sperm quality, and cause infertility. Oxidative stress is the fundamental pathogenesis of aflatoxin-induced reproductive toxicity. The overproduction of reactive oxygen substances can cause testicular failure and disturb the process of spermatogenesis. Mitochondria are susceptible to being impaired by oxidative stress, and its damage is associated with infertility. AFs also disturb the process of spermatogenesis by disrupting the regulation of genes related to the progression of the cell cycle such as cyclins and inducing genes related to apoptosis, thereby weakening fertility and negatively affecting the testicular endocrine potential by suppressing androgen synthesis. Additionally, AFs downregulate ERα expression, potentially negatively impacting spermatogenesis by enhancing the apoptotic mechanism. In this review, we provide new insights into the genotoxic and cytotoxic effects of AFB1 on the male reproductive system with a focus on the cell cycle and apoptosis destruction of testicular tissue.
黄曲霉毒素(AFs)是不可避免的环境污染物,对人类和动物健康有害。AFs 会干扰代谢过程,在肝脏中代谢为不同的羟化衍生物,同时通过机制诱导 ROS 积累、S 期停滞、DNA 损伤和细胞凋亡。长期食用受黄曲霉毒素污染的食物会对男性生殖系统造成不良影响,导致睾丸损伤,阻止睾丸酮合成,降低精子质量,并导致不孕。氧化应激是黄曲霉毒素引起生殖毒性的根本发病机制。活性氧物质的过度产生会导致睾丸衰竭并扰乱精子发生过程。线粒体容易受到氧化应激的损害,其损伤与不孕有关。AFs 还通过破坏与细胞周期进程相关的基因(如细胞周期蛋白)的调节,以及诱导与凋亡相关的基因,干扰精子发生过程,从而降低生育能力,并通过抑制雄激素合成对睾丸内分泌潜能产生负面影响。此外,AFB1 下调 ERα 的表达,可能通过增强凋亡机制对精子发生产生负面影响。在这篇综述中,我们提供了关于 AFB1 对男性生殖系统的遗传毒性和细胞毒性作用的新见解,重点是睾丸组织的细胞周期和凋亡破坏。