Melatonin Effects on Ovarian Function

Melatonin is a pleiotropic hormone renowned for its role in regulating circadian rhythms. Within the ovary it serves as a potent antioxidant and modulator of cell signalling, protecting oocytes and surrounding somatic cells against oxidative stress. Endogenously synthesised in oocytes, granulosa cells and luteal cells, melatonin concentrations in follicular fluid often exceed those in circulation. By scavenging reactive oxygen species and reinforcing mitochondrial integrity, melatonin preserves follicular viability and delays age-related decline in reproductive capacity. It influences the hypothalamic–pituitary–ovarian axis through receptor-dependent effects on gonadotrophin release, while directly supporting mitochondrial function, promoting mitophagy and reducing apoptotic pathways. Consequently, melatonin supplementation has emerged as a promising strategy to enhance oocyte quality, delay ovarian ageing and improve outcomes in assisted reproductive technologies.

Research from Nature Portfolio

Recent foundational work has demonstrated that long-term administration of melatonin in female mice attenuates age-induced ovarian decline. Treated animals exhibited larger follicle pools, extended telomere length and improved litter sizes. At a cellular level, melatonin preserved mitochondrial redox balance by decreasing mitochondrial reactive oxygen species generation, preventing collapse of membrane potential and sustaining respiratory chain enzyme activities. These effects were mediated in part through enhanced activity of SIRT3 and increased recruitment of FoxO3a to antioxidant gene promoters, culminating in reduced apoptotic signalling and maintained oocyte quality into advanced reproductive age.

Melatonin Effects on Ovarian Function publication trend

The graph below shows the total number of articles in melatonin effects on ovarian function across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen, which at high levels can damage cellular components.

Granulosa cell: Somatic cell within the ovarian follicle that supports oocyte development and hormone production.

Mitophagy: Selective autophagic process removing damaged mitochondria to maintain cellular homeostasis.

SIRT1/SIRT3: NAD⁺-dependent deacetylases that regulate mitochondrial function and stress responses.

Follicular atresia: Degenerative process leading to the breakdown of ovarian follicles that do not reach ovulation.

References

1. Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice. Scientific Reports (2016).
2. Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue. Antioxidants (2023).
3. Melatonin Attenuates Oxidative Stress-Induced Apoptosis of Bovine Ovarian Granulosa Cells by Promoting Mitophagy via SIRT1/FoxO1 Signaling Pathway. International Journal of Molecular Sciences (2023).
4. Gut microbiota–bile acid‐vitamin D axis plays an important role in determining oocyte quality and embryonic development. Clinical and Translational Medicine (2023).