Oosit Matürasyonuna Yeni Bir Bakış: N6-metiladenosin Metilasyonu

Öz

Oosit matürasyonu prenatal dönemden puberteye kadar süren birçok proteinin karşılıklı etkileşimiyle kontrol edilen bir süreçtir. Matür oositin kalitesi ileri fertilizasyon ve implantasyon başarısını doğrudan etkileyerek kaliteli embriyo oluşumuna temel oluşturmaktadır. Oositin matürasyon süreci in vivo ve in vitro ortamlarda araştırma konularından biri olup günümüzde hem sürecin anlaşılması hem de kültür ortamındaki koşulların belirlenmesine yönelik çalışmalar devam etmektedir. N6-metiladenosin (m6A) en yaygın RNA modifikasyonlarından biridir. m6A metilasyonunda metil gruplarının eklenmesinden sorumlu metiltransferazlar (yazıcılar), metil gruplarının kaldırılmasından sorumlu dimetilazlar (siliciler) ve metil grubunu bağlayıcı proteinler (okuyucular) olmak üzere üç grup protein görev almaktadır. Son yıllarda kanser, metabolik hastalıklar gibi süreçlerde önemli rolleri olduğu kanıtlanan m6A metilasyonunun oogenez ve spermatogenez süreçlerindeki yeri ve önemi de yapılan çalışmalarla ortaya çıkarılmaktadır. Bu derlemede oosit matürasyonu ve m6A metilasyonunu tanımlanması, aralarındaki ilişkinin araştırılması ve sonuçta oosit matürasyonuna m6A metilasyonu ve/veya proteinlerinin direkt/indirekt etkilerinin tartışılması amaçlanmıştır.

Anahtar Kelimeler

• Oosit Matürasyonu
• m6A Metilasyonu
• N6-metiladenosin

A New Perspective on Oocyte Maturation: N6-methyladenosine Methylation

Abstract

Oocyte maturation is a process controlled by the interaction of many proteins from the prenatal period to puberty. The quality of the mature oocyte directly affects the success of advanced fertilization and implantation and forms the basis for the formation of quality embryos. Oocyte maturation process in vivo and in vitro is one of today in research and understanding of the process is underway for determining the conditions in both the culture medium. The maturation process of the oocyte has been one of the most interesting research topics for many years, and studies are still ongoing today. N6-methyladenosine (m6A) is one of the most common RNA modifications. Three groups of proteins are involved in m6A methylation: methyltransferases (writers) responsible for adding methyl groups, dimethylases (erasers) responsible for removing methyl groups, and methyl group-binding proteins (readers). The place and importance of m6A methylation, which has been proven to have important roles in processes such as cancer and metabolic diseases in recent years, in the processes of oogenesis and spermatogenesis has also been revealed by studies. In this review, it is aimed to define oocyte maturation and m6A methylation, to investigate the relationship between them, and ultimately to discuss the direct/indirect effects of m6A methylation and/or proteins on oocyte maturation.

Keywords

• Oocyte Maturation
• m6A Methylation
• N6-methyladenosine

Kaynakça

1. Carlson, B.M, Human Embryology and Developmental Biology, 5th Edition, Saunders Elsevier, Philadelphia, 2014.
2. Delilbaşı, L, In vitro Fertilizasyon Laboratuvar Yöntemleri, Öncü Basımevi, Ankara, 2008.
3. Moore, K.L, Persaud, T.V.N, Torchia, M.G, The Developing Human: Clinically Oriented Embryology, 6th Edition, Saunders Elsevier, Philadelphia, 2008.
4. Kuyucu, Y, Tap, Ö, Oosit Olgunlaşma Süreci ve Düzenleyici Faktörler, Arşiv Kaynak Tarama Dergisi, 2009, 18 (4), 227-240.
5. Nugraha Setyawan, E.M, Oh, H.J, Kim, M.J, Kim, G.A, Lee, S.H, Choi, Y.B, Ra, K, Lee, B.C, Despite the donor's age, human adipose-derived stem cells enhance the maturation and development rates of porcine oocytes in a co-culture system, Theriogenology, 2018, 115, 57–64.
6. He, M, Zhang, T, Yang, Y, Wang, C. Mechanisms of Oocyte Maturation and Related Epigenetic Regulation, Frontiers in cell and developmental biology, 2021, 9, 654028.
7. Arroyo A, Kim B, Yeh J, Luteinizing Hormone Action in Human Oocyte Maturation and Quality: Signaling Pathways, Regulation, and Clinical Impact, Reproductive Sciences, 2020;27(6):1223-1252.
8. Sui, X, Hu, Y, Ren, C, Cao, Q, Zhou, S, Cao, Y, Li, M, Shu, W, Huo, R, METTL3-mediated m6A is required for murine oocyte maturation and maternal-to-zygotic transition, Cell Cycle, 2020, 19(4), 391–404.

9. Sun, X, Zhang, Y, Hu, Y, An, J, Li, L, Wang, Y, Zhang, X, Decreased expression of m6A demethylase FTO in ovarian aging. Archives of gynecology and obstetrics, 2021, 303(5), 1363–1369.
10. Jiang, X, Liu, B, Nie, Z, Duan, L, Xiong, Q, Jin, Z, Yang, C, Chen, Y, The role of m6A modification in the biological functions and diseases, Signal transduction and targeted therapy, 2021, 6(1), 74.
11. Fan, Y, Zhang, C, Zhu, G, Profiling of RNA N6-methyladenosine methylation during follicle selection in chicken ovary, Poultry Science, 2019, 98(11), 6117–6124.
12. Ding, C, Zou, Q, Ding, J, Ling, M, Wang, W, Li, H, Huang, B, Increased N6-methyladenosine causes infertility is associated with FTO expression, Journal of Cellular Physiology, 2018, 233(9), 7055–7066.
13. Kasowitz, S. D, Ma, J, Anderson, S.J, Leu, N.A, Xu, Y, Gregory, B.D, Schultz, R.M, Wang, P.J, Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development, PLoS Genetics, 2018, 14(5), e1007412.
14. Zhao, B.S, He, C, Gamete On for m6A: YTHDF2 Exerts Essential Functions in Female Fertility, Molecular Cell, 2017, 67(6), 903–905.
15. Wang, Y.K, Yu, X.X, Liu, Y.H, Li, X, Liu, X.M, Wang, P.C, Liu, S, Miao, J.K, Du, Z.Q, Yang, C.X, Reduced nucleic acid methylation impairs meiotic maturation and developmental potency of pig oocytes. Theriogenology, 2018, 121, 160–167.
16. Ivanova, I, Much, C, Di Giacomo, M, Azzi, C, Morgan, M, Moreira, P.N, Monahan, J, Carrieri, C, Enright, A.J, O'Carroll, D, The RNA m6A Reader YTHDF2 Is Essential for the Post-transcriptional Regulation of the Maternal Transcriptome and Oocyte Competence, Molecular cell, 2017, 67(6), 1059–1067.e4.