Primordial Follicle Regulation and Interventions for Modulating Extracellular Tension PRIME
Summary
The regulation of primordial follicle activation and dormancy is fundamental to female fertility. A woman’s follicular reserve is set at birth, with follicles remaining dormant until periodically activated. Maintaining a balance between dormancy and activation is essential for reproductive longevity. However, in conditions like premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS), this balance is disrupted, leading to infertility. Additionally, cancer patients undergoing ovarian tissue cryopreservation for fertility preservation often experience premature follicle activation upon transplantation, which reduces the functional lifespan of the graft.
Traditionally, follicle activation was considered irreversible, but recent studies suggest that mechanical forces may influence this process. Our preliminary research in mice demonstrated that exposure to mechanical pressure increased the proportion of dormant follicles, indicating a potential mechanism for regulating follicle activation. This project aims to translate these findings to human ovarian tissue, exploring whether follicular activation can be reversed or modulated through external mechanical forces. If successful, this research could revolutionize fertility preservation strategies, offering new options for women at risk of early ovarian failure or those seeking to extend their reproductive lifespan.
Objectives & Study Design
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Molecular Biomarkers of Follicle Activation – Using single-nuclei RNA sequencing (snRNA-seq) to analyze gene expression in dormant and growing follicles, identifying key markers associated with follicle activation and potential reversibility.
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Tissue Tension & Dormancy – Investigating how extracellular mechanical forces influence follicle dormancy and activation. This includes applying controlled mechanical stress to ovarian tissue and assessing changes in activation markers
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Clinical Relevance & Future Applications – Evaluating how these findings can be applied to fertility preservation strategies, particularly for patients with POI, PCOS, or those undergoing ovarian tissue transplantation.
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By understanding the molecular and mechanical factors that regulate follicle activation, this project aims to develop innovative fertility preservation techniques and challenge long-standing assumptions about ovarian biology.