Impact of Stress on Ovarian Function and Oocyte Development

Stress, whether psychological or physiological, activates the hypothalamic–pituitary–adrenal (HPA) axis and elevates circulating glucocorticoids, with profound consequences for female reproductive health. Within the ovary, stress hormones alter granulosa cell function, perturb steroidogenesis and disrupt the delicate balance of reactive oxygen species and antioxidants. These changes can trigger follicular atresia, accelerate depletion of the ovarian reserve and induce apoptosis in both somatic and germ cells. At the level of the oocyte, chronic stress can compromise cytoplasmic maturation, interfere with meiotic progression and reduce developmental competence. Key signalling pathways—including cyclic adenosine 3′,5′-monophosphate (cAMP), Fas–Fas ligand interactions and purinergic receptor activation—mediate many of these effects. Cumulus cells, as critical nurses of the oocyte, are particularly sensitive to stress‐induced inflammatory and fibrotic changes, which may further impair oocyte quality. Together, these mechanisms help explain stress‐associated subfertility and point to potential targets for therapeutic intervention aimed at preserving ovarian function and improving assisted reproductive outcomes.

Research from Nature Portfolio

A foundational study demonstrated that elevated glucocorticoid levels impair oocyte developmental potential by activating the Fas apoptotic pathway in ovarian somatic cells. In mice, systemic injection of cortisol reduced oocyte competence, lowered oestradiol–progesterone ratios and increased apoptosis in mural granulosa and cumulus cells via upregulation of Fas and Fas ligand. Mutant models lacking functional Fas ligand showed significant preservation of oocyte quality despite cortisol exposure, underlining the central role of this death‐receptor system in stress‐induced reproductive decline.

Impact of Stress on Ovarian Function and Oocyte Development publication trend

The graph below shows the total number of articles in impact of stress on ovarian function and oocyte development across all publications each year (not limited to Nature Index journals).

Technical terms

Granulosa cells: Somatic cells surrounding the developing oocyte that synthesise steroid hormones and support follicle maturation.

Cumulus cells: A specialised subset of granulosa cells forming a compact cluster around the oocyte, essential for nutrient transfer and signalling during maturation.

Ovarian reserve: The finite pool of primordial and growing follicles available for recruitment and ovulation over a woman’s reproductive lifespan.

Meiotic arrest: A reversible pause in oocyte meiosis, maintained by cAMP signalling to ensure oocyte quality until luteinising signals prompt resumption.

Glucocorticoids: Steroid hormones released in response to stress that modulate metabolism and immune responses, and at high levels can impair ovarian function.

cAMP (cyclic adenosine 3′,5′-monophosphate): A second messenger that governs oocyte dormancy and maturation by regulating protein kinase activity.

P2X7 receptor: An ATP‐gated ion channel implicated in inflammation and apoptosis, whose activation in granulosa cells disrupts cumulus expansion and ovulation.

References

1. Impact of stress on oocyte quality and reproductive outcome. Journal of Biomedical Science (2016).
2. Glucocorticoids impair oocyte developmental potential by triggering apoptosis of ovarian cells via activating the Fas system. Scientific Reports (2016).
3. Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway. Frontiers in Endocrinology (2023).
4. Role of tPA in Corticosterone-Induced Apoptosis of Mouse Mural Granulosa and Oviductal Epithelial Cells. Cells (2023).
5. Activation of P2X7 Receptor Mediates the Abnormal Ovulation Induced by Chronic Restraint Stress and Chronic Cold Stress. Biology (2024).