Rewrite Chinese Medical Journal article review explores extracellular vesicles in oocyte health and therapies this news headline for the science magazine post

The production of oocytes relies on a finely tuned network of intercellular communication pathways essential for maintaining female reproductive health. Extracellular vesicles (EVs) play an active role in this communication by transporting bioactive molecules between cells. Due to their low immunogenicity, low toxicity, and high biocompatibility, EVs have emerged as promising next-generation therapeutic agents, with demonstrated benefits across a range of conditions—from cancer to wound healing. However, their specific roles in oocyte development and ovarian disorders such as polycystic ovary syndrome (PCOS), endometriosis, ovarian ageing, and ovarian failure remain underexplored.

To address this gap, Professor Da Li and Dr. Lixia He from the Center for Reproductive Medicine, Shengjing Hospital of China, along with a team of researchers compiled a comprehensive review of EVs’ role in oocytes, under both normal physiological states and altered pathological conditions, in addition to their impact on reversing ovarian pathologies. Their findings were made available online on April 07, 2025, and published in Volume 138, Issue 9 of the Chinese Medical Journal on May 05, 2025.

“The microenvironment responsible for the production of a functional oocyte is composed of theca cells, progressively layered granulosa cells (GCs), and an antrum filled with follicular fluid. Under physiological conditions, EVs intricately orchestrate oocyte reproductive processes,” explains Prof. Li. EVs are tiny, membrane-bound nanoparticles that carry various biomolecules, including proteins, lipids, DNA, and RNA. Based on how they are formed, EVs are classified into two main types: exosomes, which are released from within the cell, and microvesicles, which bud directly from the cell membrane.

Research into follicular exosomal microRNA (miRNA) profiles reveals that EVs help regulate oocyte maturation, follicular growth, and GC proliferation. These signaling roles link EV cargo to oocyte quality in both humans and other mammals. Lipid and mRNA content within EVs further reflect the functional state of oocytes. Their role in follicle selection, the preovulatory phase, and fertilization makes EVs key intercellular communicators in reproduction.

However, in pathological conditions, EV communication becomes disrupted. EVs with altered cargo negatively impact oocyte quality and follicular health. For instance, when mouse oocytes absorbed EVs from patients with polycystic ovary syndrome (PCOS), they showed mitochondrial abnormalities and spindle dysfunction. In PCOS, EV cargo has also been linked to cholesterol transport issues, GC apoptosis, and follicular dysplasia. These EVs inhibit enzymes in the glycolysis pathway, reducing energy availability and affecting oocyte maturation.

As an inflammatory condition, PCOS is worsened by exosomes carrying pro-inflammatory molecules that alter miRNA levels, impair folliculogenesis, and lower fertilization potential—contributing to ovarian ageing. In endometriosis, where endometrial cells grow outside the uterus, EVs with overexpressed miRNAs inhibit glucose metabolism, leading to poor oocyte development. Similarly, in premature ovarian failure, abnormal EV signaling disrupts oocyte formation. Environmental exposures, such as endocrine-disrupting chemicals, also impair EV function by reducing miRNAs essential for oocyte quality. “Taken together, the contents of EVs undergo alterations under pathological conditions, leading to impaired oocyte quality and follicle health,” notes Dr. He.

Given their central role in oocyte regulation, EVs are also being explored as therapeutic tools. Exosomes derived from human umbilical cord mesenchymal stem cells have been used to deliver functional miRNAs that activate dormant follicles. In animal studies, intraovarian injections of such exosomes reduced oxidative stress and improved oocyte quality. Therapeutic EVs also show promise in preventing GC apoptosis in chemotherapy-induced ovarian failure. By delivering molecules that support hormone production and angiogenesis, EVs may help address ovarian insufficiency. In contrast, in diseases like endometriosis where excessive blood vessel formation worsens outcomes, EVs can inhibit vascular growth factors to reduce disease severity.

“Given the fascinating natural properties and engineering futures of EVs, we also highlight the therapeutic potential of EVs in reversing ovarian pathological progression, which is closely associated with the fate of oocytes and follicles,” concludes Prof. Li about the promising potential of EVs.

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Reference
DOI: 10.1097/CM9.0000000000003578