Mechanisms of Premature Ovarian Failure and Oxidative Stress

Premature ovarian failure (POF), also known as premature ovarian insufficiency, is characterised by the loss of ovarian function before the age of 40 and represents a major cause of infertility worldwide. Central to its pathogenesis is oxidative stress, a condition arising from an imbalance between reactive oxygen species (ROS) production and the body’s antioxidant defences. Excess ROS induce damage to mitochondrial DNA, proteins and lipids within ovarian somatic and germ cells, precipitating apoptosis and follicular atresia. Key molecular pathways implicated include impaired mitochondrial oxidative phosphorylation, endoplasmic reticulum stress and activation of pro-inflammatory cascades such as the NLRP3 inflammasome. Decline in critical antioxidants—among them superoxide dismutase and peroxiredoxin family members—and diminished expression of transcription factors like Nrf2 compromise cellular resilience. Concomitant disruption of survival signalling axes (for example PI3K/Akt and mTORC2) further undermines folliculogenesis, leading to depletion of the primordial follicle pool and reduced ovarian reserve. Emerging evidence also highlights telomere attrition and altered expression of gonadotrophin receptors as contributory factors. Although the precise interplay between these mechanisms remains under active investigation, therapeutic strategies aimed at restoring redox balance and supporting mitochondrial function hold promise for delaying ovarian ageing and preserving fertility.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Mechanisms of Premature Ovarian Failure and Oxidative Stress publication trend

The graph below shows the total number of articles in mechanisms of premature ovarian failure and oxidative stress across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative stress: A state in which production of reactive oxygen species exceeds antioxidant defence capacity, leading to cellular damage.

Reactive oxygen species (ROS): Highly reactive molecules containing oxygen that can damage cellular components when unregulated.

Granulosa cells: Somatic cells surrounding the oocyte within the follicle, essential for oocyte support and hormone production.

Apoptosis: Programmed cell death characterised by organised cellular dismantling, often triggered by oxidative injury in POF.

Mitochondrial oxidative phosphorylation (OXPHOS): The process by which mitochondria generate ATP through an electron transport chain and chemiosmosis.

Follicular atresia: Degeneration and resorption of ovarian follicles, a hallmark of declining ovarian reserve in POF.

References

1. Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants. Frontiers in Endocrinology (2023).
2. Nrf2 Signaling Pathway Mediates the Protective Effects of Daphnetin Against D-Galactose Induced-Premature Ovarian Failure. Frontiers in Pharmacology (2022).
3. Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation. Aging (2022).
4. Rictor/mTORC2 Pathway in Oocytes Regulates Folliculogenesis, and Its Inactivation Causes Premature Ovarian Failure*. Journal of Biological Chemistry (2015).