Hafez Hafez Mona, El-Kazaz Sara El-Sayed, El-Neweshy Mahmoud S, Shukry Mustafa, Ghamry Heba I, Tohamy Hossam G
Department of Physiology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, 22758, Egypt.
Animal and Poultry Behavior and Management, Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, Alexandria University, Alexandria, 22758, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 10. doi: 10.1007/s00210-024-03759-4.
This study investigates the protective effects of resveratrol (RSV) against heat stress (HS)-induced testicular injury in rats. Climate change has exacerbated heat stress, particularly affecting male fertility by impairing testicular function and sexual behavior. A total of 32 rats were allocated into four experimental groups: control, RSV control, HS control, and RSV + HS. The HS groups were subjected to a 43 °C water bath for 20 min to induce testicular hyperthermia, while the RSV + HS group received 20 mg/kg of RSV starting just before HS and continuing for eight weeks. Our findings reveal that HS significantly impairs male sexual behavior, evidenced by reduced mount and intromission numbers, and increased latencies. It also negatively affects the reproductive system, decreasing the weights of testes (Cohen's d = 1.8), epididymis, and accessory sex glands, and deteriorating sperm profile parameters such as motility (Cohen's d = 2.1), viability, and morphology. Furthermore, HS notably decreases reproductive performance in female rats, reducing litter size, live births, and conception rates. Biochemically, HS decreases activities of key antioxidant enzymes in the testes-glutathione peroxidase, superoxide dismutase, and catalase-while increasing lipid peroxidation, nitrite levels, and proinflammatory cytokines (IL-1β and TNF-α). It also reduces serum levels of reproductive hormones like testosterone (Cohen's d = 2.0) and 17β-estradiol. These results were affirmed with the histopathological evaluation and the immunohistochemistry staining (Ki-67, PCNA, Bax 5, and caspase-3 protein expression). Remarkably, RSV treatment mitigated these adverse effects, restoring both physiological and biochemical parameters toward normal levels (e.g., testicular weight Cohen's d = 1.6, sperm motility Cohen's d = 1.9, and testosterone levels Cohen's d = 1.7). This suggests that RSV's antioxidative, anti-inflammatory, antiapoptotic, and androgenic properties could effectively counteract the degenerative impacts of testicular hyperthermia. This highlights the potential of RSV as a therapeutic agent against climate change-induced fertility issues in males.
本研究调查了白藜芦醇（RSV）对热应激（HS）诱导的大鼠睾丸损伤的保护作用。气候变化加剧了热应激，尤其通过损害睾丸功能和性行为影响男性生育能力。总共32只大鼠被分为四个实验组：对照组、RSV对照组、HS对照组和RSV + HS组。HS组大鼠置于43°C水浴中20分钟以诱导睾丸高温，而RSV + HS组在热应激开始前即给予20mg/kg的RSV，并持续八周。我们的研究结果表明，热应激显著损害雄性性行为，表现为爬跨和插入次数减少以及潜伏期延长。它还对生殖系统产生负面影响，降低睾丸（科恩d值 = 1.8）、附睾和附属性腺的重量，并使精子特征参数如活力（科恩d值 = 2.1）、存活率和形态恶化。此外，热应激显著降低雌性大鼠的生殖性能，减少窝仔数、活产数和受孕率。生化方面，热应激降低睾丸中关键抗氧化酶——谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶的活性，同时增加脂质过氧化、亚硝酸盐水平和促炎细胞因子（IL-1β和TNF-α）。它还降低血清中睾酮（科恩d值 = 2.0）和17β-雌二醇等生殖激素的水平。这些结果通过组织病理学评估和免疫组织化学染色（Ki-67、PCNA、Bax 5和caspase-3蛋白表达）得到证实。值得注意的是，RSV治疗减轻了这些不利影响，使生理和生化参数恢复到正常水平（例如，睾丸重量科恩d值 = 1.6，精子活力科恩d值 = 1.9，睾酮水平科恩d值 = 1.7）。这表明RSV的抗氧化、抗炎、抗凋亡和雄激素特性可以有效抵消睾丸高温的退行性影响。这突出了RSV作为治疗气候变化引起的男性生育问题的治疗剂的潜力。
