<i>De novo</i> methylation in male germ cells of the common marmoset monkey occurs during postnatal development and is maintained <i>in vitro</i>

Langenstroth-Röwer, Daniel; Gromoll, Jörg; Wistuba, Joachim; Tröndle, Ina; Laurentino, Sandra; Schlatt, Stefan; Neuhaus, Nina

doi:10.1080/15592294.2016.1248007

Cited by 25 publications

(25 citation statements)

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“…Thus, defining the timing of establishment of DNA methylation throughout testicular development is crucial to investigate factors that can lead to disturbances of this process, as disease or exposure to treatments. While the majority of studies in the mouse model have shown perinatal acquisition of germ cells' DNA methylation [48,49], in non-human primates (marmoset) establishment of methylation was suggested to be a gradual process occurring during postnatal development and completed in adulthood [39]. In agreement with the primate data, our results show that in human, testicular tissue establishment of global DNA methylation of spermatogonia occurs progressively during postnatal and pubertal development.…”

Section: Discussionsupporting

confidence: 86%

“…Immunohistochemical analysis of 5-methylcytosine (5mC) revealed a progressive increase with development. Specifically, neonatal spermatogonia were predominantly unmethylated (27 ± 1.5% of methylated spermatogonia), then methylation of the spermatogonial population rose during prepubertal (39 ± 23%) and pubertal (83 ± 7.9%) stages until nearly all adult spermatogonia (97 ± 1.7%) were methylated [39].…”

Section: Introductionmentioning

confidence: 99%

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Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

Portela

Heckmann²,

Wistuba³

et al. 2020

JCM

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Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and percentage of spermatogonial subpopulation changes during development (n = 13) and due to disease and/or treatment (n = 18) in tissues stored in fertility preservation programs, using markers for spermatogonia (MAGEA4), undifferentiated spermatogonia (UTF1), proliferation (PCNA), and global DNA methylation (5mC). Throughout normal prepubertal testicular development, only the density of 5mC-positive spermatogonia significantly increased with age. In comparison, patients affected by disease and/or treatment showed a reduced density of UTF1-, PCNA- and 5mC-positive spermatogonia, whereas the percentage of spermatogonial subpopulations remained unchanged. As an exception, sickle cell disease patients treated with hydroxyurea displayed a reduction in both density and percentage of 5mC- positive spermatogonia. Our results demonstrate that, in general, a reduction in spermatogonial density does not alter the percentages of undifferentiated and proliferating spermatogonia, nor the establishment of global methylation. However, in sickle cell disease patients’, establishment of spermatogonial DNA methylation is impaired, which may be of importance for the potential use of this tissues in fertility preservation programs.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

Portela

Heckmann²,

Wistuba³

et al. 2020

JCM

Self Cite

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“…There has been discussion in literature regarding the stability of germ cell DNA methylation patterns and the role of somatic contamination in the analyzed cell fractions. A recent study in marmoset monkey revealed stable DNA methylation patterns of the H19, MEST, DDX4 and MAGEA4 genes in germ cells cultured up to 21 days [72]. Since we detected differential methylation of GO-terms related to germ cell development and in particular DNA methylation regulation of germ cell formation, there could be differences in the functionality or cellular composition of the cultured cell fractions between human and marmoset/rodent germ cell cultures.…”

Section: Plos Onementioning

confidence: 48%

Comparing genome-scale DNA methylation and CNV marks between adult human cultured ITGA6+ testicular cells and seminomas to assess in vitro genomic stability

et al. 2020

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Autologous transplantation of spermatogonial stem cells is a promising new avenue to restore fertility in infertile recipients. Expansion of the initial spermatogonial stem cell pool through cell culturing is a necessary step to obtain enough cells for effective repopulation of the testis after transplantation. Since in vitro propagation can lead to (epi-)genetic mutations and possibly malignant transformation of the starting cell population, we set out to investigate genome-wide DNA methylation status in uncultured and cultured primary testicular ITGA6+ sorted cells and compare them with germ cell tumor samples of the seminoma subtype. Seminomas displayed a severely global hypomethylated profile, including loss of genomic imprinting, which we did not detect in cultured primary testicular ITGA6+ cells. Differential methylation analysis revealed altered regulation of gamete formation and meiotic processes in cultured primary testicular ITGA6+ cells but not in seminomas. The pivotal POU5F1 marker was hypomethylated in seminomas but not in uncultured or cultured primary testicular ITGA6+ cells, which is reflected in the POU5F1 mRNA expression levels. Lastly, seminomas displayed a number of characteristic copy number variations that were not detectable in primary testicular ITGA6+ cells, either before or after culture. Together, the data show a distinct DNA methylation patterns in cultured primary testicular ITGA6+ cells that does not resemble the pattern found in seminomas, but also highlight the need for more sensitive methods to fully exclude the presence of malignant cells after culture and to further study the epigenetic events that take place during in vitro culture. PLOS ONE PLOS ONE | https://doi.org/10.1371/journal.pone.0230253 March 16, 2020 1 / 18 OPEN ACCESS Citation: Struijk RB, Dorssers LCJ, Henneman P, Rijlaarsdam MA, Venema A, Jongejan A, et al. (2020) Comparing genome-scale DNA methylation and CNV marks between adult human cultured ITGA6+ testicular cells and seminomas to assess in vitro genomic stability. PLoS ONE 15(3): e0230253. https://doi.org/10.

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“…Therefore, the methylation patterns in genic features and CpG islands of pig testis were investigated to reveal significant cytosines and associated genes for epigenetic molecular mechanisms related to male fertility. Langenstroth-Röwer et al (2017) used the marmoset monkey as the human model for testicular methylation study. They found that cytosines were predominantly unmethylated at regulatory regions of H19, LIT1, SNRPN, MEST , and OCT4 in the germ cells.…”

Section: Discussionmentioning

confidence: 99%

An Epigenome-Wide DNA Methylation Map of Testis in Pigs for Study of Complex Traits

Wang

Kadarmideen

2019

Front. Genet.

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Epigenetic changes are important for understanding complex trait variation and inheritance in pigs that are also a valuable biomedical model for human health research. Testis is the main organ for reproduction and boar taint in pigs; however, there have been no studies to-date on adult pig testis epigenome. The main objective of this study was to establish a genome-wide DNA methylation map of pig testis that would help identify candidate epigenetic biomarkers and methylated genes for complex traits such as male reproduction, fertility or boar taint. Reduced Representation Bisulfite Sequencing (RRBS) was used to study methylation levels of cytosine in nine pig testis samples. The results showed that genome-wide methylation status of nine samples overlapped greatly and their variation among pigs were low. The methylation levels of promoter, exon, intron, cytosine and guanine dinucleotide (CpG) islands and CpG island shores regions were 0.15, 0.47, 0.55, 0.39, and 0.53, respectively. Cytosines binding to CpG islands showed different methylation levels between exon and intron regions. All methylation levels of CpG islands were lower than CpG island shores in different genic features. The distribution of 12,738 differentially methylated cytosines (DMCs) within CpG islands, CpG island shores and other regions was 36.86, 21.65, and 41.49%, respectively, and was 0.33, 1.71, 5.95, and 92.01% in promoter, exon, intron and intergenic regions, respectively. Methylation levels of DMCs in promoter, exon and intron regions were significantly different between CpG islands and CpG island shores ( P < 0.05). A total of 898 genes with 2089 DMCs were enriched in 112 Gene Ontology (GO) terms. Fifteen methylated genes from our study were associated with fertility or boar taint traits. Our analysis revealed the methylation patterns in different genic features and CpG island regions of testis in pigs, and summarized several candidate genes associated with DMCs and the involved GO terms. These findings are helpful to understand the relationship between DNA methylation and genic CpG islands, to provide candidate epigenetic regions or biomarkers for pig production and welfare and for translational epigenomic studies that use pigs as an animal model for human research.

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De novo methylation in male germ cells of the common marmoset monkey occurs during postnatal development and is maintained in vitro

Cited by 25 publications

References 40 publications

Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

Comparing genome-scale DNA methylation and CNV marks between adult human cultured ITGA6+ testicular cells and seminomas to assess in vitro genomic stability

An Epigenome-Wide DNA Methylation Map of Testis in Pigs for Study of Complex Traits

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