The effect of exosomes on oocyte maturation

Turgay Barut, Hakan Darıcı, Meryem Akpolat
In: Ege Tıp Dergisi · 2025 · vol. 64(3) , pp. 563–576 · doi:10.19161/etd.1653074 · W4414072841
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Exosomes secreted by granulosa cells play a crucial regulatory role in oocyte maturation and have therapeutic potential for female infertility, especially in diminished ovarian reserve.

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This paper is a review of studies published up to September 2024 examining how exosomes (extracellular vesicles) released by ovarian granulosa cells into follicular fluid influence oocyte maturation and may contribute to infertility through mechanisms involving granulosa/cumulus cell signaling and follicular development. The authors collected evidence specifically from patient groups with premature ovarian insufficiency, diminished ovarian reserve, or polycystic ovary syndrome, while excluding male factor, tubal factor, and endometriosis. The key finding is that the existing literature portrays exosomes as having crucial regulatory roles in oocyte maturation, with potential therapeutic promise discussed as a nascent alternative approach for infertility, particularly in diminished ovarian reserve, though the review does not provide original experimental results. Relevance to endometriosis: endometriosis was explicitly excluded from the review’s included studies, so the paper’s main focus is exosomes in oocyte maturation across other infertility etiologies rather than endometriosis.

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Abstract

Aim: Numerous infertile patients face challenges in oocyte maturation during in vitro fertilization treatment. Hormonal dysregulation, mitochondrial dysfunction, abnormal organelle distribution within the ooplasm, and biological, genetic, and epigenetic factors lead to oocyte maturation arrest. Oocyte maturation involves the secretion of extracellular vesicles, known as exosomes, by surrounding granulosa cells into the follicular fluid. This review examines the mechanisms by which exosomes influence oocyte maturation, evaluates their effects on oocyte maturation in diverse female infertile patient groups, discusses the therapeutic potential of exosomes in oocyte maturation. Materials and Methods: Studies published up to September 2024 were collected from the PubMed database. The analysis methodology included the following keywords: exosome or extracellular vesicles or exosomes in reproductive medicine and oocyte maturation, diminished ovarian reserve, polycystic ovary syndrome, premature ovarian insufficiency and therapeutic potential of exosomes. This review focused on studies about exosomes in oocyte maturation and female infertility. The inclusion criteria for the studies were: studies involving patients diagnosed with (1) Premature ovarian insufficiency, (2) Diminished ovarian reserve, or (3) Polycystic ovary syndrome. Male factor infertility, tubal factor infertility, and endometriosis were excluded. Results: Existing literature demonstrates that exosomes exert crucial effects and a regulatory role on oocyte maturation. Exosomes modulate the processes of ovarian granulosa and cumulus cells to affect follicular development. Conclusion: The function of exosomes in oocyte maturation may be further clarified through detailed analysis of their specific proteins and therapeutic potential as a nascent alternative treatment for infertility, particularly in patients with diminished ovarian reserve.
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Abstract

Aim: Numerous infertile patients face challenges in oocyte maturation during in vitro fertilization treatment. Hormonal dysregulation, mitochondrial dysfunction, abnormal organelle distribution within the ooplasm, and biological, genetic, and epigenetic factors lead to oocyte maturation arrest. Oocyte maturation involves the secretion of extracellular vesicles, known as exosomes, by surrounding granulosa cells into the follicular fluid. This review examines the mechanisms by which exosomes influence oocyte maturation, evaluates their effects on oocyte maturation in diverse female infertile patient groups, discusses the therapeutic potential of exosomes in oocyte maturation.

Materials and methods

Studies published up to September 2024 were collected from the PubMed database. The analysis methodology included the following keywords: exosome or extracellular vesicles or exosomes in reproductive medicine and oocyte maturation, diminished ovarian reserve, polycystic ovary syndrome, premature ovarian insufficiency and therapeutic potential of exosomes. This review focused on studies about exosomes in oocyte maturation and female infertility. The inclusion criteria for the studies were: studies involving patients diagnosed with (1) Premature ovarian insufficiency, (2) Diminished ovarian reserve, or (3) Polycystic ovary syndrome. Male factor infertility, tubal factor infertility, and endometriosis were excluded.

Results

Existing literature demonstrates that exosomes exert crucial effects and a regulatory role on oocyte maturation. Exosomes modulate the processes of ovarian granulosa and cumulus cells to affect follicular development.

Conclusion

The function of exosomes in oocyte maturation may be further clarified through detailed analysis of their specific proteins and therapeutic potential as a nascent alternative treatment for infertility, particularly in patients with diminished ovarian reserve.

Keywords

Project Number N/A Ethical Statement Bu çalışmanın, özgün bir çalışma olduğunu; çalışmanın hazırlık, veri toplama, analiz ve bilgilerin sunumu olmak üzere tüm aşamalarından bilimsel etik ilke ve kurallarına uygun davrandığımı; bu çalışma kapsamında elde edilmeyen tüm veri ve bilgiler için kaynak gösterdiğimi ve bu kaynaklara kaynakçada yer verdiğimi; kullanılan verilerde herhangi bir değişiklik yapmadığımı, çalışmanın Committee on Publication Ethics (COPE)' in tüm şartlarını ve koşullarını kabul ederek etik görev ve sorumluluklara riayet ettiğimi beyan ederim. Herhangi bir zamanda, çalışmayla ilgili yaptığım bu beyana aykırı bir durumun saptanması durumunda, ortaya çıkacak tüm ahlaki ve hukuki sonuçlara razı olduğumu bildiririm. Thanks Bu çalışmayı yapma isteğimi destekleyen ve katkıda bulunan Tez Danışman'ın Prof.Dr. Meryem Akpolat Ferah ve tez çalışma sürecimde laboratuvarlarını bana açan eski kurumum Memorial Hastanesi IVF Merkezine ve Dr.Öğr. Üyesi Hakan Darıcı'ya, bu süreçte yaptığı değerli çalışmalarıyla bana her zaman örnek olan ve beni bu alanda çalışmaya cesaretlendiren hocam Prof.Dr. Yiğit Uyanıkgil'e, ayrıca yayınımın değerlendirilme sürecinde ilk üniversitem olan Ege Üniversite'si bünyesindeki Ege Tıp Dergisi editörü ve yayın kurulu üyelerine teşekkürü bir borç bilirim.

References

- Welsh JA, Goberdhan DCI, O’Driscoll L, Buzas EI, Blenkiron C, Bussolati B, et al. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J Extracell Vesicles. 2024 Feb 1;13(2):1–84. - Tkach M, Théry C. Communication by Extracellular Vesicles: Where We Are and Where We Need to Go. Cell. 2016 Mar 10;164(6):1226–32. - Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, et al. Vesiclepedia: A Compendium for Extracellular Vesicles with Continuous Community Annotation. PLoS Biol. 2012 Dec;10(12). - Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009 Aug 5;9(8):581–93. - El Andaloussi S, Mäger I, Breakefield XO, Wood MJA. Extracellular vesicles: Biology and emerging therapeutic opportunities. Vol. 12, Nature Reviews Drug Discovery. 2013. p. 347–57. - Doyle LM, Wang MZ. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Vol. 8, Cells. MDPI; 2019. p. 1–24. - Raposo G, Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. Vol. 200, Journal of Cell Biology. 2013. p. 373–83. - Lee Y, El Andaloussi S, Wood MJA. Exosomes and microvesicles: Extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet. 2012 Oct;21(R1):125–34. Details Primary Language English Subjects Histology and Embryology, Reproductive Medicine (Other) Journal Section Review Publication Date September 8, 2025 Submission Date March 7, 2025 Acceptance Date May 9, 2025 Published in Issue Year 2025 Volume: 64 Number: 3 APA Barut, T., Darici, H., & Akpolat Ferah, M. (2025). The effect of exosomes on oocyte maturation. Ege Tıp Dergisi, 64(3), 563-576. https://doi.org/10.19161/etd.1653074 AMA 1.Barut T, Darici H, Akpolat Ferah M. The effect of exosomes on oocyte maturation. EJM. 2025;64(3):563-576. doi:10.19161/etd.1653074 Chicago Barut, Turgay, Hakan Darici, and Meryem Akpolat Ferah. 2025. “The Effect of Exosomes on Oocyte Maturation”. Ege Tıp Dergisi 64 (3): 563-76. https://doi.org/10.19161/etd.1653074. EndNote Barut T, Darici H, Akpolat Ferah M (September 1, 2025) The effect of exosomes on oocyte maturation. Ege Tıp Dergisi 64 3 563–576. IEEE [1]T. Barut, H. Darici, and M. Akpolat Ferah, “The effect of exosomes on oocyte maturation”, EJM, vol. 64, no. 3, pp. 563–576, Sept. 2025, doi: 10.19161/etd.1653074. ISNAD Barut, Turgay - Darici, Hakan - Akpolat Ferah, Meryem. “The Effect of Exosomes on Oocyte Maturation”. Ege Tıp Dergisi 64/3 (September 1, 2025): 563-576. https://doi.org/10.19161/etd.1653074. JAMA 1.Barut T, Darici H, Akpolat Ferah M. The effect of exosomes on oocyte maturation. EJM. 2025;64:563–576. MLA Barut, Turgay, et al. “The Effect of Exosomes on Oocyte Maturation”. Ege Tıp Dergisi, vol. 64, no. 3, Sept. 2025, pp. 563-76, doi:10.19161/etd.1653074. Vancouver 1.Turgay Barut, Hakan Darici, Meryem Akpolat Ferah. The effect of exosomes on oocyte maturation. EJM. 2025 Sep. 1;64(3):563-76. doi:10.19161/etd.1653074

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