Search

Background: In mammalian females, progressive activation of dormant primordial follicles in adulthood is crucial for the maintenance of the reproductive lifespan. Misregulated activation of primordial follicles leads to various ovarian diseases, such as premature ovarian insufficiency (POI). Although recent studies have revealed that several functional genes and pathways, such as phosphoinositide 3-kinase (PI3K) signaling, play roles in controlling the activation of primordial follicles, our understanding of the molecular networks regulating the activation progress is still incomplete., Results: Here, we identify a new role for cell division cycle 42 (CDC42) in regulating the activation of primordial follicles in mice. Our results show that CDC42 expression increases in oocytes during the activation of primordial follicles in the ovary. Disruption of CDC42 activity with specific inhibitors or knockdown of Cdc42 expression significantly suppresses primordial follicle activation in cultured mouse ovaries. Conversely, the follicle activation ratio is remarkably increased by overexpression of CDC42 in ovaries. We further demonstrate that CDC42 governs the process of primordial follicle activation by binding to phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (p110β) and regulating the expression levels of PTEN in oocytes. Finally, we extend our study to potential clinical applications and show that a short-term in vitro treatment with CDC42 activators could significantly increase the activation rates of primordial follicles in both neonatal and adult mouse ovaries., Conclusion: Our results reveal that CDC42 controls the activation of primordial follicles in the mammalian ovary and that increasing the activity of CDC42 with specific activators might improve the efficiency of in vitro activation approaches, opening avenues for infertility treatments.

Ovarian fibrosis, characterized by the excessive proliferation of ovarian fibroblasts and the accumulation of extracellular matrix (ECM), serves as one of the primary causes of ovarian dysfunction. Despite the critical role of ovarian fibrosis in maintaining the normal physiological function of the mammalian ovaries, research on this condition has been greatly underestimated, which leads to a lack of clinical treatment options for ovarian dysfunction caused by fibrosis. This review synthesizes recent research on the molecular mechanisms of ovarian fibrosis, encompassing TGF-β, extracellular matrix, inflammation, and other profibrotic factors contributing to abnormal ovarian fibrosis. Additionally, we summarize current treatment approaches for ovarian dysfunction targeting ovarian fibrosis, including antifibrotic drugs, stem cell transplantation, and exosomal therapies. The purpose of this review is to summarize the research progress on ovarian fibrosis and to propose potential therapeutic strategies targeting ovarian fibrosis for the treatment of ovarian dysfunction. [ABSTRACT FROM AUTHOR]

Background: Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. Methods: Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. Results: After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. Conclusions: Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice. [ABSTRACT FROM AUTHOR]