Insulin-like growth factor 1 as a key paracrine mediator in mesenchymal stem cell-based intervention for ovarian ageing: a review

Ovarian ageing refers to the progressive functional decline and structural degeneration of the ovary with advancing age, primarily manifested as a reduction in both the quantity and quality of follicles. These changes lead to decreased female fertility, increased miscarriage rates, and elevated risks of age-related diseases. Current treatments cannot fundamentally promote ovarian regeneration. Mesenchymal stem cells (MSCs) possess properties such as self-renewal and paracrine signalling, and their transplantation can restore ovarian function, with the paracrine pathway being a key mechanism. Insulin-like growth factor 1 (IGF-1), a peptide growth factor secreted by MSCs, regulates ovarian cell proliferation, differentiation, and survival through pathways like PI3K/Akt and Ras/Raf/MEK/ERK. To summarize and critically evaluate the latest research progress on the role of MSC-secreted IGF-1 in restoring ovarian function. IGF-1 is an important mediator through which MSCs ameliorate ovarian ageing, improving ovarian tissue structure, hormone secretion, and fertility in preclinical models. However, most evidence remains preclinical, and future work should address the translational challenges, including safety, efficacy, and the precise role of IGF-1 within the complex MSCs paracrine network.