Spermatogenesis, an intricate process occurring in the testis, is responsible for ongoing production of spermatozoa and thus the cornerstone of lifelong male fertility. In the testis, spermatogenesis occurs optimally at a temperature 2-4°C lower than that of the core body. Increased scrotal temperature generates testicular heat stress and later causes testicular atrophy and spermatogenic arrest, resulting in a lower sperm yield and therefore impaired male fertility. Melatonin (N-acetyl-5-methoxytryptamine), a small neuro-hormone synthesized and secreted by the pineal gland and the testis, is widely known as a potent free-radical scavenger; it has been reported that melatonin protects the testis against inflammation and reactive oxygen species generation thereby playing anti-inflammatory, -oxidative and -apoptotic roles in the testis. Nevertheless, the role of melatonin in the testicular response to heat stress has not been studied. Here, by employing a mouse model of testicular hyperthermia, we systematically investigated the testicular response to heat stress as well as the occurrence of autophagy, apoptosis and oxidative stress in the testis. Importantly, we found that pre-treatment with melatonin attenuated heat-induced apoptosis and oxidative stress in the testis. Also, post-treatment with melatonin promoted recovery of the testes from heat-induced damage, probably by maintaining the integrity of the Sertoli cell tight-junction. Thus, we for the first time provide the proof of concept that melatonin can protect the testis against heat-induced damage, supporting the potential future use of melatonin as a therapeutic drug in men for sub/infertility incurred by various testicular hyperthermia factors.

中文翻译：

---

褪黑素可保护小鼠睾丸免受热损伤。

精子发生是睾丸中发生的一个复杂过程，是精子持续产生的原因，因此也是终生男性生育的基石。在睾丸中，精子发生最佳发生在比核心体温度低2-4°C的温度下。阴囊温度升高会产生睾丸热应激，随后引起睾丸萎缩和生精停滞，从而导致精子产量降低，从而影响男性的生育能力。褪黑激素（N-乙酰基-5-甲氧基色胺）是一种由松果体和睾丸合成和分泌的小神经激素，众所周知是一种有效的自由基清除剂。据报道，褪黑素保护睾丸免受炎症和活性氧的产生，从而在睾丸中发挥抗炎，氧化和凋亡的作用。不过，尚未研究褪黑激素在睾丸对热应激反应中的作用。在这里，通过采用小鼠睾丸热疗模型，我们系统地研究了睾丸对热应激的反应以及睾丸中自噬，细胞凋亡和氧化应激的发生。重要的是，我们发现褪黑素预处理可减轻睾丸中热诱导的细胞凋亡和氧化应激。同样，褪黑激素的后处理可能通过维持Sertoli细胞紧密连接的完整性促进了睾丸从热诱导的损伤中恢复。因此，我们首次提供了褪黑激素可以保护睾丸免受热损伤的概念验证，