Md Mokhtar Amir Hafidz, Malik Ifrah Alam, Abd Aziz Noor Azean Anis, Almabhouh Fayez A, Durairajanayagam Damayanthi, Singh Harbindar Jeet
Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh, Selangor, Malaysia.
I-PPerForM , Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh, Selangor, Malaysia.
Andrologia. 2019 Apr;51(3):e13196. doi: 10.1111/and.13196. Epub 2018 Nov 19.
This study examined the effects of PI3K and AMPK signalling pathway inhibitors on leptin-induced adverse effects on rat spermatozoa. Sprague-Dawley rats, aged 14-16 weeks, were randomised into control, leptin-, leptin + dorsomorphin (AMPK inhibitor)-, and leptin+LY294002 (PI3K inhibitor)-treated groups with six rats per group. Leptin was given once daily for 14 days via the intraperitoneal (i.p.) route at a dose of 60 ug kg body weight. Rats in the leptin and inhibitor-treated groups received concurrently either dorsomorphin (5 mg kg day ) or LY294002 (1.2 mg kg day ) i.p. for 14 days. Controls received 0.1 ml of normal saline. Upon completion, sperm count, sperm morphology, seminiferous tubular epithelial height (STEH), seminiferous tubular diameter (STD), 8-hydroxy-2-deoxyguanosine (8-OHdG) and phospho-Akt/total Akt ratio were estimated. Data were analysed using ANOVA. Sperm count, STEH and STD were significantly lower, while the percentage of spermatozoa with abnormal morphology and the level of 8-OHdG were significantly higher in rats treated with leptin and leptin + dorsomorphin when compared to those in controls and LY294002-treated rats. Testicular phospho-Akt/total Akt ratio was significantly higher in leptin and leptin + LY294002-treated rats. In conclusion, LY294002 prevents leptin-induced changes in rat sperm parameters, suggesting the potential role of the PI3K signalling pathway in the adverse effects of leptin on sperm parameters.
本研究考察了PI3K和AMPK信号通路抑制剂对瘦素诱导的大鼠精子不良反应的影响。将14 - 16周龄的Sprague-Dawley大鼠随机分为对照组、瘦素处理组、瘦素 + dorsomorphin（AMPK抑制剂）处理组和瘦素 + LY294002（PI3K抑制剂）处理组，每组6只大鼠。通过腹腔注射途径，以60 μg/kg体重的剂量每天给瘦素处理14天。瘦素处理组和抑制剂处理组的大鼠同时腹腔注射dorsomorphin（5 mg/kg·天）或LY294002（1.2 mg/kg·天），持续14天。对照组注射0.1 ml生理盐水。实验结束后，估计精子计数、精子形态、生精小管上皮高度（STEH）、生精小管直径（STD）、8-羟基-2-脱氧鸟苷（8-OHdG）和磷酸化Akt/总Akt比值。数据采用方差分析进行分析。与对照组和LY294002处理组的大鼠相比，瘦素处理组和瘦素 + dorsomorphin处理组的大鼠精子计数、STEH和STD显著降低，而形态异常的精子百分比和8-OHdG水平显著升高。瘦素处理组和瘦素 + LY294002处理组的大鼠睾丸磷酸化Akt/总Akt比值显著升高。总之，LY294002可预防瘦素诱导的大鼠精子参数变化，提示PI3K信号通路在瘦素对精子参数的不良反应中具有潜在作用。
