Ovarian Aging and Follicle Dynamics
Summary
The human ovary undergoes a progressive decline in both quantity and quality of its follicle pool from the moment of birth until menopause. Ovarian ageing encompasses a complex interplay of cellular, molecular and systemic processes that culminate in diminished fertility, altered hormone production and increased risk of metabolic and cardiovascular comorbidities. At the heart of this process lies the dynamic balance between the activation of dormant primordial follicles and their loss through atresia. Hormonal cues, notably follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and local growth factors, govern recruitment and growth of follicles via signalling pathways such as PI3K/AKT and SMAD. Meanwhile, accumulating oxidative stress, mitochondrial dysfunction and epigenetic changes compromise granulosa cell support and oocyte competence. Stromal remodelling and collagen deposition further alter the ovarian microenvironment, reinforcing follicular attrition. Understanding these intertwined mechanisms has global significance: it informs fertility counselling, underpins development of interventions to extend reproductive lifespan and sheds light on women’s health in later life.
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Ovarian Aging and Follicle Dynamics publication trend
The graph below shows the total number of articles in ovarian aging and follicle dynamics across all publications each year (not limited to Nature Index journals).
Technical terms
Ovarian reserve: The total pool of primordial and growing follicles available in the ovary at any given age.
Primordial follicle activation (PFA): The transition of dormant primordial follicles into the growing cohort under local and endocrine signals.
Atresia: The process of programmed cell death and degeneration of follicles that do not reach ovulation.
Ferroptosis: A regulated form of cell death driven by iron-dependent lipid peroxidation.
Mitochondrial homeostasis: The dynamic equilibrium of mitochondrial biogenesis, fission–fusion cycles and mitophagy essential for cellular energy production.
m6A methylation: A reversible chemical modification of RNA that influences stability, splicing and translation, impacting granulosa cell ageing.
References
- Metabolic Mechanisms and Potential Therapeutic Targets for Prevention of Ovarian Aging: Data from Up-to-Date Experimental Studies. International Journal of Molecular Sciences (2023).
- Bone Marrow Mesenchymal Stem Cells Reversed Ovarian Aging-related m6A RNA Methylation Modification Profile in Aged Granulosa Cells. Stem Cell Reviews and Reports (2023).
- ErZhiTianGui Decoction alleviates age-related ovarian aging by regulating mitochondrial homeostasis and inhibiting ferroptosis. Journal of Ovarian Research (2024).
- Human Ovarian Reserve from Conception to the Menopause. PLOS ONE (2010).
- Tubulointerstitial nephritis antigen‐like 1 deficiency alleviates age‐dependent depressed ovulation associated with ovarian collagen deposition in mice. Reproductive Medicine and Biology (2019).
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