On fertility again: Dose–Response Effects of Oral Melatonin on Reproductive Parameters in Intact Male Pomeranian Dogs With Alopecia X: A Controlled Study 2025
This study investigates the dose–response effects of oral melatonin on reproductive parameters in intact male Pomeranian dogs diagnosed with Alopecia X. Given melatonin’s potential therapeutic effects on hair regrowth and reproductive health, this study aimed to evaluate its impact on semen quality, hormonal profiles and testicular haemodynamics. A total of 16 intact male Pomeranian dogs were randomly assigned to four groups: a control group receiving a placebo and three treatment groups receiving melatonin at low (0.1 mg/kg), medium (0.3 mg/kg) and high (0.5 mg/kg) doses, administered twice daily for 45 days. Reproductive parameters, including semen volume, sperm concentration, total sperm count, sperm motility and levels of testosterone and oestradiol 17-ß, were assessed biweekly. Testicular haemodynamics were evaluated using pulsed Doppler ultrasonography. The results showed dose-dependent improvements in semen quality and testicular blood flow, with the highest dose group demonstrating the most significant improvements. However, analysis of the testosterone-to-oestradiol ratio revealed a decrease in the treatment groups, highlighting a complex hormonal response. Although semen quality improved, the study’s short duration may not have captured the full spermatogenesis cycle. These findings suggest that melatonin may enhance reproductive function in male dogs with Alopecia X, but further research is needed to clarify its long-term endocrine effects and optimize treatment protocols.
When comparing the different doses of melatonin, the dose-dependent improvements in semen parameters suggest that higher doses, such as 0.5 mg/kg, are more effective in optimizing semen quality. However, despite these improvements, the lack of significant changes in the testosterone-to-oestradiol ratio, even at higher doses, raises important questions regarding the long-term safety and efficacy of high-dose melatonin. Prolonged high-dose administration may affect hormonal feedback mechanisms and other endocrine functions. Furthermore, our study provides a deeper understanding of melatonin’s mechanisms, suggesting that melatonin may exert its effects through antioxidant properties and by influencing the hypothalamic–pituitary–gonadal axis, as well as potentially acting locally within the testes (Mogheiseh et al. 2022). The enhancement of testicular blood flow could also play a crucial role in supporting healthy spermatogenesis. However, further research is necessary to explore the long-term effects of melatonin on reproductive health, optimize dosing regimens and investigate its detailed mechanisms, including its role in local hormone modulation and blood flow dynamics within the testes.
And potential for rapa + melatonin combination? Melatonin enhances everolimus efficacy in breast cancer by suppressing mTOR pathway activation and promoting apoptosis and mitochondrial function 2025
To investigate the effects of melatonin and everolimus combination, we divided MCF-7 cells into four experimental groups: the control, Melatonin (3 mM), Everolimus (30 nM), and a combination of Melatonin and Everolimus (3 mM + 30 nM). Cell viability, apoptosis, autophagy activation, and mitochondrial function were evaluated using established techniques.
Based on the cell viability test, the combination of 30 nM everolimus and 3 mM melatonin inhibited phosphorylation of 4E-BP1 and p70S6K, which are downstream effectors of the mTOR pathway, and reduced cell growth. In addition, co-administration of melatonin and everolimus increased apoptosis and led to Sub-G1 phase accumulation. LC3 protein expression and LC3 puncta analysis demonstrated autophagic activity. In terms of mitochondrial function, co-administration of melatonin with everolimus did not cause proton leakage or mitochondrial uncoupling, but did restore everolimus-induced respiratory inhibition.
In conclusion, melatonin is thought to improve the effectiveness of everolimus by inhibiting mTOR downstream effectors, enhancing apoptosis, activating autophagy, improving mitochondrial respiration, and reducing MCF-7 growth.
