Oocyte Aging and Oxidative Stress Mechanisms

Oocyte ageing is a time‐dependent decline in the quality and developmental competence of the female gamete. Central to this deterioration is oxidative stress, arising when reactive oxygen species (ROS) overwhelm the oocyte’s antioxidant defences. Mitochondrial dysfunction, impaired DNA repair and reduced proteostasis combine to exacerbate macromolecular damage, chromosomal segregation errors and epigenetic alterations. Key regulators of redox balance such as the NAD+‐dependent sirtuin family become less active with age, compromising histone deacetylation and organelle homeostasis. Consequent calcium dysregulation, retrotransposon activation and proteasome‐mediated protein degradation further accelerate the decline. These processes not only reduce fertilisation and embryo development rates in assisted reproductive technologies but may also impair offspring health. Understanding the interplay between oxidative insults and the oocyte’s intrinsic repair systems has global significance for fertility preservation, livestock breeding and developmental biology.

Research from Nature Portfolio

Studies have demonstrated that supplementation of antioxidants during in vitro culture of immature oocytes can preserve nuclear maturation, mitochondrial function and spindle integrity. By scavenging ROS and maintaining DNA integrity, antioxidants extend the window of competence for fertilisation and minimise chromosomal aberrations. In porcine models, application of astaxanthin during postovulatory culture significantly restored mitochondrial membrane potential, reduced apoptosis and autophagic activity, and supported organelle distribution, leading to improved blastocyst formation. These findings highlight the potential for targeted antioxidant therapies to stabilise redox homeostasis and delay the onset of ageing‐associated defects in mammalian oocytes.

Oocyte Aging and Oxidative Stress Mechanisms publication trend

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

Technical terms

Oocyte: A female gamete or egg cell that undergoes meiosis and, upon fertilisation, gives rise to an embryo.

Oxidative stress: Imbalance between the production of reactive oxygen species and the capacity of antioxidant defences, leading to cellular damage.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen, such as superoxide and hydrogen peroxide, which can damage lipids, proteins and DNA.

Mitochondria: Organelles responsible for ATP production and regulation of apoptosis, acting as both a source and target of ROS.

Sirtuins (SIRT): A family of NAD+‐dependent deacetylases that regulate chromatin structure, metabolism and stress responses in oocytes and somatic cells.

Proteasome: A protein complex that degrades ubiquitinated proteins, maintaining proteostasis and removing damaged or misfolded proteins.

References

1. Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage. Oxidative Medicine and Cellular Longevity (2017).
2. Protective effect of antioxidants on the pre-maturation aging of mouse oocytes. Scientific Reports (2017).
3. Inhibitory effects of astaxanthin on postovulatory porcine oocyte aging in vitro. Scientific Reports (2020).
4. Diminished NAD+ levels and activation of retrotransposons promote postovulatory aged oocyte (POAO) death. Cell Death Discovery (2024).
5. The Antioxidant Salidroside Ameliorates the Quality of Postovulatory Aged Oocyte and Embryo Development in Mice. Antioxidants (2024).
6. Single-Cell Multi-Omics Analysis of In Vitro Post-Ovulatory–Aged Oocytes Revealed Aging-Dependent Protein Degradation. Molecular & Cellular Proteomics (2024).