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The effect of exosomes on oocyte maturation

Yıl 2025, Cilt: 64 Sayı: 3, 563 - 576, 08.09.2025

Turgay Barut , Hakan Darici , Meryem Akpolat Ferah

https://doi.org/10.19161/etd.1653074

Öz

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.

Anahtar Kelimeler

Extracellular Vesicle Exosome Oocyte Maturation Diminished Ovarian Reserve Polycystic Ovarian Syndrome

Proje Numarası

N/A

Kaynakça

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  • 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).
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  • 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.
  • Khalyfa A, Gaddameedhi S, Crooks E, Zhang C, Li Y, Qiao Z, et al. Circulating exosomal MiRNAs signal circadian misalignment to peripheral metabolic tissues. Int J Mol Sci. 2020 Sep 1;21(17):1–25.
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  • Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007 Jun;9(6):654–9.
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Eksozomların oosit Maturasyonu'na etkisi

Yıl 2025, Cilt: 64 Sayı: 3, 563 - 576, 08.09.2025

Turgay Barut , Hakan Darici , Meryem Akpolat Ferah

https://doi.org/10.19161/etd.1653074

Öz

Amaç: Çok sayıda infertil hasta, in vitro fertilizasyon tedavisi sırasında oosit olgunlaşma sürecinde zorluk yaşamaktadır. Hormonal düzensizlik, mitokondriyal disfonksiyon, ooplazma içinde anormal organel dağılımı, biyolojik, genetik ve epigenetik faktörler oosit maturasyonunun durmasına neden olmaktadır. Oosit maturasyonu sürecinde etrafını çevreleyen granüloza hücrelerinden eksozom olarak bilinen ekstraselüler veziküllerin folikül sıvısına salınımı gerçekleşmektedir. Bu derlemede oosit maturasyonunu eksozomların hangi mekanizmalarla etkilediği incelenmekte, çeşitli kadın infertil hasta gruplarında oosit maturasyonu üzerindeki etkileri değerlendirilmekte ve eksozomların oosit maturasyonundaki terapötik potansiyelleri ortaya konulmaktadır.
Gereç ve Yöntem: Eylül 2024'e kadar yayınlanmış çalışmalar PubMed veri tabanından toplanmıştır. Arama stratejisi aşağıdaki anahtar kelimeleri içermiştir: eksozom veya ekstrasellüler veziküller veya üreme tıbbında eksozomlar ve oosit olgunlaşması ve azalmış over rezervi ve polikistik over sendromu ve erken over yetmezliği ve eksozomların terapötik potansiyeli. Bu derleme, eksozomların kadın faktörüne bağlı infertilitede oosit olgunlaşmasındaki rolünü araştıran çalışmalara odaklanmıştır. Çalışmalar için dâhil edilme kriterleri: (1) Erken over yetmezliği, (2) Azalmış over rezervi veya (3) Polikistik over sendromu tanısı almış hastaları içeren çalışmalar olmuştur. Erkek faktörüne bağlı infertilite, tubal faktöre bağlı infertilite ve endometriozis üzerine odaklanan çalışmalar hariç tutulmuştur.
Bulgular: Mevcut literatür incelememiz, eksozomların oosit maturasyonu üzerinde önemli etkileri olduğunu ve düzenleyici bir rol oynadığını ortaya koymaktadır. Kanıtlar, eksozomların foliküler gelişimi etkilemek için ovaryan granüloza ve kumulus hücrelerinin fonksiyonlarını düzenlediğini göstermektedir.
Sonuç: Eksozomların spesifik proteinlerinin ayrıntılı analizi ile oosit maturasyonundaki rolü daha detaylı aydınlatılabilir. Özellikle azalmış over rezervine sahip hastalarda infertilite tedavisinde gelecekte alternatif bir terapötik potansiyele sahip olduklarını düşündürmektedir.

Anahtar Kelimeler

Ekstraselüler Vezikül Eksozom Oosit Maturasyonu Azalmış Over Rezervi Polikistik Over Sendromu

Etik Beyan

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.

Proje Numarası

N/A

Teşekkür

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.

Kaynakça

  • 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.
  • Khalyfa A, Gaddameedhi S, Crooks E, Zhang C, Li Y, Qiao Z, et al. Circulating exosomal MiRNAs signal circadian misalignment to peripheral metabolic tissues. Int J Mol Sci. 2020 Sep 1;21(17):1–25.
  • Chen H, Wang L, Zeng X, Schwarz H, Nanda HS, Peng X, et al. Exosomes, a New Star for Targeted Delivery. Vol. 9, Frontiers in Cell and Developmental Biology. Frontiers Media S.A.; 2021. p. 1–20.
  • Goto T, Fujiya M, Konishi H, Sasajima J, Fujibayashi S, Hayashi A, et al. An elevated expression of serum exosomal microRNA-191, - 21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker. BMC Cancer. 2018 Jan 31;18(116):1–11.
  • Yamamoto H. Detection of DNA methylation of gastric juice-derived exosomes in gastric cancer. Integr Mol Med. 2014 Sep 24;1(2):17–21.
  • Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007 Jun;9(6):654–9.
  • Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Vol. 30, Annual review of cell and developmental biology. 2014. p. 255–89.
  • Kowalczyk A, Wrzecińska M, Czerniawska-Piątkowska E, Kupczyński R. Exosomes – Spectacular role in reproduction. Vol. 148, Biomedicine and Pharmacotherapy. Elsevier Masson s.r.l.; 2022. p. 1–12.
  • Wortzel I, Dror S, Kenific CM, Lyden D. Exosome-Mediated Metastasis: Communication from a Distance. Vol. 49, Developmental Cell. Cell Press; 2019. p. 347–60.
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  • Shomali N, Hemmatzadeh M, Yousefzadeh Y, Soltani-Zangbar MS, Hamdi K, Mehdizadeh A, et al. Exosomes: Emerging biomarkers and targets in folliculogenesis and endometriosis. Vol. 142, Journal of Reproductive Immunology. Elsevier Ireland Ltd; 2020. p. 1–11.
  • da Silveira JC. Follicular fluid exosomes contain miRNAs capable of modulating the bovine cumulus-oocyte complex transcriptome. Scientific report. 2012 Feb;623–623.
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  • Boots CE, Jungheim ES. Inflammation and Human Ovarian Follicular Dynamics. Semin Reprod Med. 2015 Jul 3;33(4):270–5.
  • Liu Y, Liu H, Li Z, Fan H, Yan X, Liu X, et al. The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients via Altering the Follicular Microenvironment. Front Immunol. 2021 May 17;12(12):1–14.
  • Tong M, Chamley LW. Placental extracellular vesicles and feto-maternal communication. Cold Spring Harb Perspect Med. 2015 Sep 15;5(3):1–18.
  • Matsuno Y, Onuma A, Fujioka YA, Yasuhara K, Fujii W, Naito K, et al. Effects of exosome-like vesicles on cumulus expansion in pigs in vitro. Nara; 2017 Feb.
  • Xu L, Sun H, Zhang M, Jiang Y, Zhang C, Zhou J, et al. MicroRNA-145 protects follicular granulosa cells against oxidative stress-induced apoptosis by targeting Krüppel-like factor 4. Mol Cell Endocrinol. 2017 Sep 5;452:138–47.
  • Collado-Fernandez E, Picton HM, Dumollard Ré. Metabolism throughout follicle and oocyte development in mammals. International Journal of Developmental Biology. 2012;56(10–12):799–808.
  • Salomon C, Das S, Erdbrügger U, Kalluri R, Kiang Lim S, Olefsky JM, et al. Extracellular Vesicles and Their Emerging Roles as Cellular Messengers in Endocrinology: An Endocrine Society Scientific Statement. Endocr Rev. 2022 Jun 1;43(3):441–68.
  • Hung WT, Navakanitworakul R, Khan T, Zhang P, Davis JS, McGinnis LK, et al. Stage-specific follicular extracellular vesicle uptake and regulation of bovine granulosa cell proliferation. Biol Reprod. 2017 Oct 1;97(4):644–55.
  • Brännströ M, Enskog A. Leukocyte networks and ovulation [Internet]. Vol. 57, Journal of Reproductive Immunology. 2002. Available from: www.elsevier.com/locate/jreprimm
  • Zhou R, Liu D. The function of exosomes in ovarian granulosa cells. Vol. 394, Cell and Tissue Research. Springer Science and Business Media Deutschland GmbH; 2023. p. 257–67.
  • Song H, Liu B, Dong B, Xu J, Zhou H, Na S, et al. Exosome-Based Delivery of Natural Products in Cancer Therapy. Vol. 9, Frontiers in Cell and Developmental Biology. Frontiers Media S.A.; 2021. p. 1–10.
  • Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. Journal of Controlled Release. 2015 Jun 10;207:18–30.
  • Fu S, Wang Y, Xia X, Zheng JC. Exosome engineering: Current progress in cargo loading and targeted delivery. Vol. 20, NanoImpact. Elsevier B.V.; 2020.
  • Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. Journal of Controlled Release. 2015 Jan 6;205:35–44.
  • Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. Journal of Controlled Release. 2015 May;205:35–44.
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  • Zhang S, Huang B, Su P, Chang Q, Li P, Song A, et al. Concentrated exosomes from menstrual blood-derived stromal cells improves ovarian activity in a rat model of premature ovarian insufficiency. Stem Cell Res Ther. 2021 Dec 1;12(1):1–16.
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  • Sun B, Ma Y, Wang F, Hu L, Sun Y. miR-644-5p carried by bone mesenchymal stem cell-derived exosomes targets regulation of p53 to inhibit ovarian granulosa cell apoptosis. Stem Cell Res Ther. 2019 Nov 29;10(1):1–9.
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  • Yu L, Wang C, Zhang D, Liu M, Liu T, Pan B, et al. Exosomal circ_0008285 in follicle fluid regulates the lipid metabolism through the miR-4644/ LDLR axis in polycystic ovary syndrome. J Ovarian Res. 2023 Dec 1;16(1):2–14.
  • Zhao Y, Tao M, Wei M, Du S, Wang H, Wang X. Mesenchymal stem cells derived exosomal miR-323-3p promotes proliferation and inhibits apoptosis of cumulus cells in polycystic ovary syndrome (PCOS). Artif Cells Nanomed Biotechnol. 2019 Dec 4;47(1):3804–13.
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  • Touraine P, Chabbert-Buffet N, Plu-Bureau G, Duranteau L, Sinclair AH, Tucker EJ. Premature ovarian insufficiency. Nat Rev Dis Primers. 2024 Sep 12;10(1):63.
  • Bao S, Yin T, Liu S. Ovarian aging: energy metabolism of oocytes. Vol. 17, Journal of Ovarian Research . BioMed Central Ltd; 2024.
  • Zhu Q, Li Y, Ma J, Ma H, Liang X. Potential factors result in diminished ovarian reserve: a comprehensive review. Vol. 16, Journal of Ovarian Research. BioMed Central Ltd; 2023.
  • Chen Z, Wang X. The Role and Application of Exosomes and Their Cargos in Reproductive Diseases: A Systematic Review. Vol. 9, Veterinary Sciences. MDPI; 2022.
  • Pillay P, Moodley K, Moodley J, Mackraj I. Placenta-derived exosomes: Potential biomarkers of preeclampsia. Vol. 12, International Journal of Nanomedicine. Dove Medical Press Ltd.; 2017. p. 8009–23.
  • Sun B, Peng J, Wang S, Liu X, Zhang K, Zhang Z, et al. Applications of stem cell-derived exosomes in tissue engineering and neurological diseases. Rev Neurosci. 2018 Jul 26;29(5):531–46.
  • Zhang Z, Shi C, Wang Z. The physiological functions and therapeutic potential of exosomes during the development and treatment of polycystic ovary syndrome. Vol. 14, Frontiers in Physiology. Frontiers Media SA; 2023.
Toplam 81 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Histoloji ve Embriyoloji, Üreme Tıbbı (Diğer)
Bölüm Derlemeler
Yazarlar

Turgay Barut 0000-0001-5915-9292

Hakan Darici 0000-0001-9393-554X

Meryem Akpolat Ferah 0000-0002-3419-1728

Proje Numarası N/A
Yayımlanma Tarihi 8 Eylül 2025
Gönderilme Tarihi 7 Mart 2025
Kabul Tarihi 9 Mayıs 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 64 Sayı: 3

Kaynak Göster

Vancouver Barut T, Darici H, Akpolat Ferah M. The effect of exosomes on oocyte maturation. ETD. 2025;64(3):563-76.
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