Importance: Ovarian aging has become a focal point in current research on female aging and refers to the gradual decline in ovarian function as women age. Numerous factors influence ovarian aging, among which mitochondrial function is one because it plays a crucial role by affecting oocytes and granulosa cells. Mitochondrial deterioration not only leads to a decrease in oocyte quality but also hinders follicle development, further impacting women's reproductive health and fertility.
Objective: This review summarizes and integrates research on the impact of mitochondrial function on ovarian aging, outlining the mechanisms by which mitochondria regulate the functions of oocytes and granulosa cells. This study aims to provide potential therapeutic directions to mitigate mitochondrial decline and support female reproductive health.
Evidence Review: According to a 2023 study published in Cell, factors such as oxidative stress, mitochondrial dysfunction, chronic inflammation, and telomere shortening collectively drive ovarian aging, directly affecting female fertility. Among these factors, mitochondrial dysfunction plays a key role. This study reviewed literature from databases such as PubMed, Google Scholar, and CNKI, using keywords such as "mitochondrial dysfunction", "decline in oocyte quality and quantity", and "ovarian aging", aiming to summarize current research on the mechanisms of the impact of mitochondrial dysfunction on ovarian aging and provide theoretical support for future exploration of related therapeutic strategies.
Findings: The main characteristics of ovarian aging include a decline in oocyte quantity and quality, fluctuations in hormone levels, and a reduction in granulosa cell function. Studies have shown that mitochondria affect fertility by regulating cellular energy metabolism, exacerbating oxidative stress, causing mitochondrial DNA (mtDNA) damage, and impacting the physiological function of granulosa cells within the ovary, gradually diminishing the ovarian reserve.
Conclusion: This review focuses on analyzing the effects of mitochondrial decline on energy production in oocytes and granulosa cells, the accumulation of reactive oxygen species (ROS), and the calcium ion (Ca) concentration, which all contribute to the ovarian aging process, and understanding them will provide new insights into the mechanisms of ovarian aging.
Relevance: Therapeutic interventions targeting mitochondrial dysfunction may help delay ovarian aging and improve female reproductive health.
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http://dx.doi.org/10.1186/s12967-025-06223-w | DOI Listing |
Cells
February 2025
NUS Bia-Echo Asia Centre of Reproductive Longevity and Equality, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
The ovary is a dynamic organ where mechanical forces profoundly regulate follicular development, oocyte maturation, and overall reproductive function. These forces, originating from the extracellular matrix (ECM), granulosa and theca cells, and ovarian stroma, influence cellular behavior through mechanotransduction, translating mechanical stimuli into biochemical responses. This review explores the intricate interplay between mechanical cues and ovarian biology, focusing on key mechanosensitive pathways such as Hippo signaling, the PI3K/AKT pathway, and cytoskeletal remodeling, which govern follicular dormancy, activation, and growth.
View Article and Find Full Text PDFReprod Biomed Online
November 2024
IVIRMA Global Research Alliance, IVIRMA Madrid, Spain; Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain, and Rey Juan Carlos University, Madrid, Spain.
With a growing number of women in developed countries having children later in life, it is time to rethink women's reproductive health. This trend of 'delayed parenthood' reflects a complex interplay of labour market rules, personal choices, rarefying social connections and the renowned possibilities of assisted reproductive technology (ART). While ART offers support, its success wanes with age, prompting a rise in additional strategies such as elective ovarian cryopreservation.
View Article and Find Full Text PDFWomen carrying the fragile X premutation (55-200 CGG repeat expansion, PM) are at risk for developing fragile X-associated primary ovarian insufficiency (FXPOI), which is preceded by fragile X-associated diminished ovarian reserve (FXDOR). So far, the cause of FXDOR/FXPOI could not be comprehensively examined due to the scarcity of human ovarian tissue and oocytes. From studies in model systems, it was proposed that molecular abnormalities within the ovaries or a diminished primordial follicle pool cause FXDOR/FXPOI.
View Article and Find Full Text PDFDue to the extended period for clinical diagnosis, the etiology of endometriotic lesion initiation is not well understood or characterized. Endometriotic lesions are most often found on pelvic tissues and organs, especially the ovaries. To investigate the role of tissue tropism on ovarian endometrioma initiation, we adapted a well-characterized polyacrylamide microarray system to investigate the role of tissue-specific extracellular matrix and adhesion motifs on endometriotic cell attachment, morphology, and size.
View Article and Find Full Text PDFDecline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women ( . osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!