Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Life Sci. 2021 Aug 1;278:119605. doi: 10.1016/j.lfs.2021.119605. Epub 2021 May 11.
Diabetes mellitus (DM) may lead to testicular-related infertility while Myristic acid (MA) is beneficial to lower hyperglycaemia. Thus, we hypothesized that MA could protect testes against hyperglycaemia-induced damage in DM. DM was induced in adult male rats by high-fat diet consumption for 12 weeks, accompanied by a single dose streptozotocin injection. Following DM confirmation, the rats were fed orally with 10 and 20 mg/kg body weight MA for 28 consecutive days. After completion of treatment, rats were sacrificed and blood, cauda epididymis and testes were harvested. Serum was separated, epididymal sperm was collected for analysis. Molecular studies of the testes were performed by qPCR, Western blotting and immunostaining. MA was found to protect the testes against oxidative stress via preventing the upregulation of RAGE, Keap1, and the downregulation of Nrf2, NQO1, HO1, SOD, CAT and GPx. MA also prevented increase in testicular inflammation and apoptosis, as indicated by low inflammatory (NF-κB p65, IKKβ, TNF-α, IL-1β and iNOS) and apoptosis (Bax and caspase-9), but high anti-apoptosis (Bcl-2) markers' levels. Besides, MA prevented the downregulation of testicular steroidogenic markers (3βHSD, 17βHSD, StAR, ARA-54 and CYP11A1). Sperm analysis revealed near normal sperm count, motility, viability, lower abnormal sperm morphology in diabetic rats received MA. MA also prevented the loss of germ cells via preventing the decreased in cell proliferative marker (PCNA) while maintaining near normal epithelial height, tubular and Leydig cell diameters in the testes in DM. MA protects the testes against damage in DM, thus maintaining spermatogenesis and steroidogenesis, consequently preserving male fertility in diabetes.
糖尿病（DM）可能导致与睾丸相关的不育，而肉豆蔻酸（MA）有利于降低高血糖。因此，我们假设 MA 可以保护睾丸免受糖尿病引起的高血糖损伤。通过高脂饮食喂养 12 周并单次注射链脲佐菌素诱导成年雄性大鼠发生 DM。确认 DM 后，大鼠连续 28 天口服 10 和 20mg/kg 体重的 MA。治疗完成后，处死大鼠并采集血液、附睾尾和睾丸。分离血清，收集附睾精子进行分析。通过 qPCR、Western blot 和免疫染色对睾丸进行分子研究。MA 通过防止 RAGE、Keap1 上调和 Nrf2、NQO1、HO1、SOD、CAT 和 GPx 下调来保护睾丸免受氧化应激。MA 还通过降低炎症（NF-κB p65、IKKβ、TNF-α、IL-1β 和 iNOS）和凋亡（Bax 和 caspase-9）标志物水平，同时升高抗凋亡（Bcl-2）标志物水平来防止睾丸炎症和凋亡增加。此外，MA 防止睾丸类固醇生成标志物（3βHSD、17βHSD、StAR、ARA-54 和 CYP11A1）下调。精子分析显示，接受 MA 的糖尿病大鼠的精子计数、活力、存活率接近正常，畸形精子形态减少。MA 还通过防止细胞增殖标志物（PCNA）减少来防止生殖细胞丢失，同时保持 DM 中睾丸上皮高度、管状和莱迪希细胞直径接近正常。MA 可保护睾丸免受 DM 损伤，从而维持精子发生和类固醇生成，进而维持糖尿病雄性的生育能力。
