DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells

Liao, Hua‐Fang; Chen, Wendy S.C.; Chen, Yu Hsiang; Kao, Tzu Hao; Tseng, Yen Tzu; Lee, Chien Yueh; Chiu, Yi-Chang; Lee, Pei Lung; Lin, Qing; Ching, Yung Hao; Hata, Kenichiro; Cheng, Weijia; Tsai, Mong-Hsun; Sasaki, Hidetada; Ho, Hong Nerng; Wu, Shinn-Chih; Huang, Yen-Hua; Yen, Pauline H.; Lin, Shau Ping

doi:10.1242/dev.105130

Cited by 50 publications

(49 citation statements)

References 87 publications

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“…In a previous study, DNMT3L was expressed only in germ cells, and the expression pattern was observed in males and females (77). However, in males, DNMT3L was initially detected at 12.5 days after fertilization of the egg, and the levels peaked at 15.5 days and remained upregulated until birth (77)(78)(79). However, the expression of DNMT3L was significantly 79 following birth and was found to be low in mature germ cells (36)(37)(38), suggesting an association between DNMT3L and DNA methylation.…”

Section: Dna Methylation and Spermatogenesismentioning

confidence: 84%

“…In certain individuals with deletion mutations in DNMT genes, a proportion of the paternal differentially methylated regions (DMRs) were normal, which suggested that DNMTs have some functional duplication (77)(78)(79). Notably, oocytes lacking DNMT3L were able to undergo normal meiosis and exhibited methylation of repeat sequences; however, a significant lack of methylation-mediated imprinting existed only in the female imprinting positions (48)(49)(50)(51)(52).…”

Section: Dna Methylation and Spermatogenesismentioning

confidence: 99%

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DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Infertility is a significant problem for human reproduction, with males and females equally affected. However, the molecular mechanisms underlying male infertility remain unclear. Spermatogenesis is a highly complex process involving mitotic cell division, meiosis cell division and spermiogenesis; during this period, unique and extensive chromatin and epigenetic modifications occur to bring about specific epigenetic profiles in spermatozoa. It has recently been suggested that the dysregulation of epigenetic modifications, in particular the methylation of sperm genomic DNA, may serve an important role in the development of numerous diseases. The present study is a comprehensive review on the topic of male infertility, aiming to elucidate the association between sperm genomic DNA methylation and poor semen quality in male infertility. In addition, the current status of the genetic and epigenetic determinants of spermatogenesis in humans is discussed. Contents1. Introduction 2. DNA methylation 3. DNA methylation and spermatogenesis 4. DNA methylation and genomic imprinting 5. DNA methylation and male infertility 6. Conclusion IntroductionEpigenetics is the study of genomic structural modifications that affect gene expression without altering the underlying nucleotide sequence (1-3). Epigenetic mechanisms involved in the regulation of gene expression include the regulation of non-coding RNA, chromatin remodeling, DNA methylation and histone modifications (4,5). Of these mechanisms, DNA methylation has been implicated in numerous biological functions, such as the development of spermatozoa and early embryos, and the repression of endogenous retrotransposons, while it also has a wide range of effects in gene expression (2,3,6). The dysregulation of DNA methylation has previously been associated with various human disorders, and has been shown to increase the risk of fertilization failure, dysfunction in embryogenesis, perinatal mortality, congenital abnormalities, preterm birth and low birth weight (7-11). The present review assesses the significance of DNA methylation in spermatogenesis in order to elucidate the association between the dysregulation of DNA methylation and male infertility. This may provide a basis for the prevention and treatment of male infertility, as well as permit the evaluation of the epigenetic quality of sperm in order to reduce the risk of epigenetic diseases in cases where conception is performed by assisted reproductive technology (ART). DNA methylationEpigenetic mechanisms are critical regulators of gene expression during spermatogenesis that may influence male fertility (12-14). Cytosine, a key DNA base, is methylated at the position, typically in the context of CpG dinucleotides. The methylation of constitutive heterochromatic and promoter regions is generally associated with reduced gene transcription (Fig. 1A) (15-18). Therefore, DNA methylation is a type of epigenetic modification that can effectively promote gene silencing (Fig. 1B). The methyl group for this chemical modif...

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Section: Dna Methylation and Spermatogenesismentioning

confidence: 84%

Section: Dna Methylation and Spermatogenesismentioning

confidence: 99%

DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

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“…DNA methyltransferase 3-like (DNMT3L) is involved in SSC quiescence. DNMT3L positively regulates the stability of promyelocytic leukemia zinc finger (PLZF) in THY1 C SSCs through down-regulating CDK2 expression, which may degrade PLZF through the ubiquitin pathway (Liao et al 2014). The distal CpG island of Cdk2 promoter has been shown to be hypomethylated in Dnmt3l-knockout SSCs compared to the wide-type cells (Liao et al 2014).…”

Section: Dna Methylation and Ssc Division And Differentiationmentioning

confidence: 99%

“…DNMT3L positively regulates the stability of promyelocytic leukemia zinc finger (PLZF) in THY1 C SSCs through down-regulating CDK2 expression, which may degrade PLZF through the ubiquitin pathway (Liao et al 2014). The distal CpG island of Cdk2 promoter has been shown to be hypomethylated in Dnmt3l-knockout SSCs compared to the wide-type cells (Liao et al 2014). On the other hand, it has been reported that the expression of DNMT3a2 and DNMT3b is undetectable in PLZF-positive and KIT-negative SSCs (Shirakawa et al 2013 members of DNMT3 subfamily in regulating mitotic self-renewal of mouse SSCs.…”

Section: Dna Methylation and Ssc Division And Differentiationmentioning

confidence: 99%

MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis

Yao¹,

Liu²,

Sun³

et al. 2015

Reproduction

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Spermatogenesis is composed of three distinctive phases, which include self-renewal of spermatogonia via mitosis, spermatocytes undergoing meiosis I/II and post-meiotic development of haploid spermatids via spermiogenesis. Spermatogenesis also involves condensation of chromatin in the spermatid head before transformation of spermatids to spermatozoa. Epigenetic regulation refers to changes of heritably cellular and physiological traits not caused by modifications in the DNA sequences of the chromatin such as mutations. Major advances have been made in the epigenetic regulation of spermatogenesis. In this review, we address the roles and mechanisms of epigenetic regulators, with a focus on the role of microRNAs and DNA methylation during mitosis, meiosis and spermiogenesis. We also highlight issues that deserve attention for further investigation on the epigenetic regulation of spermatogenesis. More importantly, a thorough understanding of the epigenetic regulation in spermatogenesis will provide insightful information into the etiology of some unexplained infertility, offering new approaches for the treatment of male infertility.Reproduction (2015) 150 R25-R34

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“…Thus, the competition between PLZF and SALL4 is an important topic of investigation. It has been recently shown by Liao et al (2014) that reduced levels of PLZF in Dnmt3l-knockout Thy1 C cells results in the releases of the PLZF antagonist SALL4, which is associated with maintaining the delicate balance of cycling and quiescent SSCs/progenitor cells. Further study is required to investigate whether SALL4 C / PLZF K A single and A paired spermatogonia are destined to differentiate.…”

Section: Introductionmentioning

confidence: 99%

Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling

Chen¹,

Liu²

2015

Reproduction

234

166

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Spermatogenesis is a continuous and productive process supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs), which arise from undifferentiated precursors known as gonocytes and are strictly controlled in a special 'niche' microenvironment in the seminiferous tubules. Sertoli cells, the only somatic cell type in the tubules, directly interact with SSCs to control their proliferation and differentiation through the secretion of specific factors. Spermatocyte meiosis is another key step of spermatogenesis, which is regulated by Sertoli cells on the luminal side of the blood-testis barrier through paracrine signaling. In this review, we mainly focus on the role of Sertoli cells in the regulation of SSC self-renewal and spermatocyte meiosis, with particular emphasis on paracrine and endocrine-mediated signaling pathways. Sertoli cell growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), as well as Sertoli cell transcription factors, such as ETS variant 5 (ERM; also known as ETV5), nociceptin, neuregulin 1 (NRG1), and androgen receptor (AR), have been identified as the most important upstream factors that regulate SSC self-renewal and spermatocyte meiosis. Other transcription factors and signaling pathways (GDNF-RET-GFRA1 signaling, FGF2-MAP2K1 signaling, CXCL12-CXCR4 signaling, CCL9-CCR1 signaling, FSH-nociceptin/OPRL1, retinoic acid/FSH-NRG/ERBB4, and AR/RB-ARID4A/ARID4B) are also addressed.Reproduction (2015) 149 R159-R167

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DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells

Cited by 50 publications

References 87 publications

DNA methylation in spermatogenesis and male infertility

DNA methylation in spermatogenesis and male infertility

MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis

Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling

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