Introduction
‘’Melatonin protects the mouse testis against heat-induced damage’’ (Zhang et al, 2020) is the review paper at this week’s ESHRE Twitter journal club.
In a nutshell (no pun intended) the authors found that pre-treatment with melatonin attenuated heat-induced apoptosis (cell death) & oxidative stress in the testis & post-treatment promoted recovery of the testes from heat-induced damage, probably by maintaining the integrity of the Sertoli cell tight-junction. Therefore, for the first time, providing 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.
This correlates with a recent study by Riviere et al (published Sept 2020), in which Melatonin oral supplementation not only increased its own testicular levels but also decreased inflammation- and oxidative stress-related markers levels, and improved the tubular wall aspect.
Spermatogenesis & temperature
Spermatogenesis is a temperature-dependent process, occurring optimally at a temperature 2–4◦C lower than that of the core body.
Increases in scrotal temperature lead to heat stress & can disrupt sperm production: an increase of 1◦C can result in a 14% decline in spermatogenesis
Testes in most mammals are in the scrotum, outside the body & are 2–8°C below core body temperature. In addition, the temperature within the testis is regulated by a counter current heat exchange system
Causes of testicular heat stress
Factors that may contribute towards testicular heat stress are;
- lifestyle and behavioural causes such as clothing, posture (sitting for long periods or sitting cross legged), heated seats, hot baths & saunas, cycling, obesity & laptop use.
- Occupational and environmental factors such as job exposure e.g. welders, bakers etc, professional or occupational drivers & men with long daily seated commutes
- Clinical factors such as Cryptorchidism (failure of the testis to fully descend into the scrotal sac before birth or within the first few months of life), Varicocele (affects 15% of the male population, 40% of men with primary infertility & 8 out of 10 men with secondary infertility) & febrile episodes (fever)
Melatonin & the Testes
Melatonin is a natural hormone produced by the pineal gland (pinecone shaped gland in the brain); darkness prompts it to start producing melatonin while light causes production to stop. It basically tells the body that its dark outside.
It is also a potent antioxidant, scavenging free radicals, interacting with the immune system as an anti-inflammatory & affecting gene expression
In the Testes melatonin is able to promote testicular development by modulating testosterone secretion, FSH action and proliferation and differentiation of testicular somatic cells and germ cells
Melatonin oral supplementation & testicular development
Riviere et al have previously shown an inverse correlation between testicular melatonin concentration and inflammation/oxidative stress-related markers levels in infertile men showing unexplained azoospermia
Their recent study (published Sept 2020) evaluated the impact of melatonin oral supplementation (daily 3 mg dose used to treat sleep disorders) on the incidence of local inflammation, oxidative stress, and tubular wall fibrosis development in young and middle-aged infertile adult men. Compared with testes without histological alterations, gonads with morphological abnormalities showed lower melatonin concentration along with increased macrophage numbers, TBARS generation, and expression levels of inflammation-related markers and antioxidant enzymes, as well as tubular wall collagen fibers disorganization and thickening.
Melatonin oral supplementation not only increased its own testicular levels but also decreased inflammation- and oxidative stress-related markers levels, and improved the tubular wall aspect.
Their work provides insights into the potential benefits of melatonin on the inflammatory and oxidative status in testes of patients suffering from unexplained infertility.
References
Melatonin daily oral supplementation attenuates inflammation and oxidative stress in testes of men with altered spermatogenesis of unknown aetiology. Riviere. E et al. Molecular & Cellular Endocrinology Vol 515, 15 September 2020, https://doi.org/10.1016/j.mce.2020.110889
