Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance

2010 ◽  
pp. n/a-n/a ◽  
Author(s):  
Hendrik Wermann ◽  
Hans Stoop ◽  
Ad JM Gillis ◽  
Friedemann Honecker ◽  
Ruud JHLM van Gurp ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Cisplatin Resistance ◽  
Global Dna Methylation ◽  
Germ Cell Tumours

Abstract LB-67: Global DNA methylation in fetal human germ cells and germ cell tumors: correlation with differentiation and cisplatin resistance

2010 ◽  
Author(s):  
Leendert H.J Looijenga ◽  
Hendrik Wermann ◽  
Ad Gillis ◽  
Friedemann Honecker ◽  
Ole Ammerpohl ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Cisplatin Resistance ◽  
Germ Cell Tumors ◽  
Global Dna Methylation

Gobal DNA methylation in fetal human germ cells and germ cell tumors: correlation with differentiation and cisplatin resistance

2010 ◽  
Vol 203 (1) ◽  
pp. 64
Author(s):  
Leendert Looijenga ◽  
Hendrik Wermann ◽  
Hans Stoop ◽  
Ad Gillis ◽  
Friedemann Honecker ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Cisplatin Resistance ◽  
Germ Cell Tumors

P–529 Whole-genome methylation analysis of testicular germ cells from cryptozoospermic men points to recurrent and functionally relevant DNA methylation changes

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S D Persio ◽  
E Leitão ◽  
M Wöste ◽  
T Tekath ◽  
J F Cremers ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Small Sample ◽  
Global Dna Methylation ◽  
Obstructive Azoospermia ◽  
Whole Genome ◽  
Ploidy Analysis ◽  
Normal Spermatogenesis

Abstract Study question Do DNA methylation changes occur in testicular germ cells (TGCs) from patients with impaired spermatogenesis? Summary answer TGCs from men with cryptozoospermia exhibit altered DNA methylation levels at several genomic regions, many of which are associated with genes involved in spermatogenesis. What is known already In the last 15 years, several studies have described DNA methylation changes in sperm of infertile men. More recently, using whole genome bisulfite sequencing (WGBS) we were able to refute these findings by demonstrating that somatic DNA contamination and genetic variation confound methylation studies in swim-up purified sperm of severely oligozoospermic men. However, it remains unknown whether altered DNA methylation plays a role during the development of the germ cells in the testes of these patients. Study design, size, duration For identifying DNA methylation differences associated with impaired spermatogenesis, we compared the TGC methylomes of men with cryptozoospermia (CZ) and men with obstructive azoospermia (n = 4 each), who had normal spermatogenesis and served as controls (CTR). Study participants were selected among an age-matched cohort of 24 CTR and 10 CZ. The selection was based on similar composition of the TGC suspension evaluated by ploidy analysis and absence of somatic DNA. Participants/materials, setting, methods TGCs were isolated from biopsies after short-term cell culture. Presence of somatic DNA was evaluated by analyzing the DNA methylation levels of H19, MEST, DDX4 and XIST. WGBS was performed at ∼14× coverage. Bioinformatic tools were used to compare global DNA methylation levels, identify differentially methylated regions (DMRs) and functionally annotate the DMRs. Single-cell RNA sequencing (scRNA-seq) was used to associate the DNA methylation changes to gene expression. Main results and the role of chance We could not identify any difference in the global DNA methylation level or at imprinted regions between CZ and CTR samples. However, using stringent filters to identify group-specific methylation differences, we detected 271 DMRs, 238 of which were hypermethylated in CZ (binominal test, p < 2.2 × 10–16). The DMRs are associated with 132 genes, 61 of which are known to be differentially expressed at various stages of spermatogenesis according to scRNA-seq studies. Almost all of the DMRs associated with the 61 genes are hypermethylated in CZ (63/67, p = 1.107 × 10–14). As assessed by scRNA-seq, 13 DMR-associated genes, which were mainly expressed during meiosis and spermiogenesis, show a significantly different pattern of expression in CZ patients. In four of these genes, the promoter was hypermethylated in CZ men, which correlates with a lower expression level in these patients. In the other nine genes, most of which downregulated in CZ, germ cell-specific enhancers may be affected. Limitations, reasons for caution The small sample size constitutes a limitation of this study. Furthermore, even though the cellular composition of samples was similar by ploidy analysis, we cannot rule out that the observed DNA methylation changes might be due to differences in the relative proportion of different germ cell types. Wider implications of the findings: Impaired spermatogenesis is associated with DNA methylation changes in testicular germ cells at functionally relevant regions of the genome, which points to an important role of DNA methylation in normal spermatogenesis. The DNA methylation changes may contribute to premature abortion of spermatogenesis and therefore not appear in mature sperm. Trial registration number N/A

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

scholarly journals Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

2013 ◽  
Vol 57 (2-3-4) ◽  
pp. 309-317 ◽  
Author(s):  
Dina G. Kristensen ◽  
Niels E. Skakkebk ◽  
Ewa Rajpert-De Meyts ◽  
Kristian Almstrup
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Germ Cell Tumours ◽  
Testicular Germ Cell ◽  
Testicular Germ Cell Tumours

scholarly journals Differences in DNA methylation profiles by histologic subtype of paediatric germ cell tumours: a report from the Children’s Oncology Group

2018 ◽  
Vol 119 (7) ◽  
pp. 864-872 ◽  
Author(s):  
Lindsay A. Williams ◽  
Lauren Mills ◽  
Anthony J. Hooten ◽  
Erica Langer ◽  
Michelle Roesler ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cell Tumours ◽  
Oncology Group ◽  
Histologic Subtype
Sign in / Sign up

Export Citation Format

Share Document