Critical roles of mRNA m6A modification and YTHDC2 expression for meiotic initiation and progression in female germ cells

Zeng, Ming; Dai, Xin; Liang, Ziwen; Sun, Ruliang; Huang, Sui; Luo, Lixia; Li, Zhongxiang

doi:10.1016/j.gene.2020.144810

Cited by 18 publications

(17 citation statements)

References 23 publications

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“…A large number of alternative splicing deficiency in oocytes [48] YTHDC2 Adult female mice with YTHDC2 gene knockout were infertile YTHDC2 suppressed expression of the meiotic markers and affected the percent of FGCs at zygotene [50] YTHDF2/ 3 Double mutation of YTHDF2 and YTHDF3 resulted in impaired female gonad development Failure of m6A modified mRNA degradation [52] Erasers FTO The decrease of FTO mRNA and protein expression caused high risk POI / [53] FGCs: female germ cells; POI: premature ovarian insufficiency; So far, few reviews have addressed m6A in relation to female reproductive health. Hence, we summarize and focus on the role of m6A modification and its protein machineries in oogenesis and female reproductive system diseases including tumors and PCOS and so on.…”

Section: / [46]mentioning

confidence: 99%

Role of m6A modification in female infertility and reproductive system diseases

Chen

Fang

et al. 2022

Int. J. Biol. Sci.

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Gamete abnormalities and reproductive system tumors have become a dominant cause of infertility, troubling people globally. In recent years, increasing evidence emerged and found that N6-methyladenosine (m6A) played a leading role in reproduction. The biological effects of m6A modification are dynamically and reversibly regulated by methyltransferases (writers), WTAP, METTL3, METTL14 and KIAA1429, demethylases (erasers), FTO and ALKBH5, and m6A binding proteins (readers), including YTH domain. In this review, we highlight the change of m6A modification in abnormal oogenesis, female reproductive system diseases including reproductive system tumors, adenomyosis, endometriosis, premature ovarian failure and polycystic ovary syndrome. Moreover, we review some of the mechanisms and the specific modified genes that have been identified. Especially, with the underlying mechanisms being uncovered, m6A and its protein machineries are expected to be the markers and targets for the diagnosis and treatment of female reproductive dysfunction.

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Section: / [46]mentioning

confidence: 99%

Role of m6A modification in female infertility and reproductive system diseases

Chen

Fang

et al. 2022

Int. J. Biol. Sci.

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“…YTHDC1 is required in oocyte growth and maturation and YTHDC1-deficient oocytes are blocked at the primary follicle stage [ 35 ]. YTHDC2 and YTHDF2 are also essential for the meiotic initiation and progression of female germ cells [ 34 , 40 ]. In the current study, we found the number of m 6 A methylated genes was higher in the granulosa cells of older women with decreased ovarian reserve, [ 41 ]which was consistent with increased m 6 A levels that Sun et al reported [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve

Liu

Yang

et al. 2022

BMC Genomics

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Background The emerging epitranscriptome plays an essential role in female fertility. As the most prevalent internal mRNA modification, N6-methyladenine (m6A) methylation regulate mRNA fate and translational efficiency. However, whether m6A methylation was involved in the aging-related ovarian reserve decline has not been investigated. Herein, we performed m6A transcriptome-wide profiling in the ovarian granulosa cells of younger women (younger group) and older women (older group). Results m6A methylation distribution was highly conserved and enriched in the CDS and 3’UTR region. Besides, an increased number of m6A methylated genes were identified in the older group. Bioinformatics analysis indicated that m6A methylated genes were enriched in the FoxO signaling pathway, adherens junction, and regulation of actin cytoskeleton. A total of 435 genes were differently expressed in the older group, moreover, 58 of them were modified by m6A. Several specific genes, including BUB1B, PHC2, TOP2A, DDR2, KLF13, and RYR2 which were differently expressed and modified by m6A, were validated using qRT-PCR and might be involved in the decreased ovarian functions in the aging ovary. Conclusions Hence, our finding revealed the transcriptional significance of m6A modifications and provide potential therapeutic targets to promote fertility reservation for aging women.

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“…YTHDC2 may promote the metastasis of colon cancer by promoting the translation of HIF-1α, and YTHDC2 may be a diagnostic marker and target gene for the treatment of colon cancer (Tanabe et al, 2016). Zeng et al (2020) suggest that mRNA m6A modification and YTHDC2 expression are crucial to meiotic initiation and progression in female germ cells. And YTHDC2 also regulates the transition from proliferation to differentiation of germline (Bailey et al, 2017).…”

Section: Demethylases ("Erasers")mentioning

confidence: 99%

Role of RNA N6-Methyladenosine Modification in Male Infertility and Genital System Tumors

Liu

Lao

Wang

et al. 2021

Front. Cell Dev. Biol.

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Epigenetic alterations, particularly RNA methylation, play a crucial role in many types of disease development and progression. Among them, N6-methyladenosine (m6A) is the most common epigenetic RNA modification, and its important roles are not only related to the occurrence, progression, and aggressiveness of tumors but also affect the progression of many non-tumor diseases. The biological effects of RNA m6A modification are dynamically and reversibly regulated by methyltransferases (writers), demethylases (erasers), and m6A binding proteins (readers). This review summarized the current finding of the RNA m6A modification regulators in male infertility and genital system tumors and discussed the role and potential clinical application of the RNA m6A modification in spermatogenesis and male genital system tumors.

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Critical roles of mRNA m6A modification and YTHDC2 expression for meiotic initiation and progression in female germ cells

Cited by 18 publications

References 23 publications

Role of m6A modification in female infertility and reproductive system diseases

Role of m6A modification in female infertility and reproductive system diseases

Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve

Role of RNA N6-Methyladenosine Modification in Male Infertility and Genital System Tumors

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