Expression Profiling of Mammalian Male Meiosis and Gametogenesis Identifies Novel Candidate Genes for Roles in the Regulation of Fertility

Schlecht, Ulrich; Demougin, Philippe; Koch, R; Hermida, Leandro; Wiederkehr, Christa; Descombes, Patrick; Pineau, Charles; Jégou, Bernard; Primig, Michael

doi:10.1091/mbc.e03-10-0762

Cited by 119 publications

(103 citation statements)

References 75 publications

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“…It is unique among integrated databases because it is focused on specific biological components and processes that play roles in germ-cell biology. It also provides access to microarray and image data relevant to the knowledge base [Schlecht et al, 2004;Zhou et al, 2005;Hermida et al, 2006]. Future goals for GermOnline include adding capacity to curate data on protein-DNA interactions and SNPs, and adding video and other types of image data.…”

Section: Bioinformatics Tools In Germ-cell Analysesmentioning

confidence: 99%

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Wyrobek

Mulvihill

Wassom

et al. 2007

Environ and Mol Mutagen

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Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in ~5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ-cell mutagens, no human germ-cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ-cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility. A multidisciplinary workshop responding to this challenge convened at The Jackson Laboratory in Bar Harbor, Maine. The purpose of the workshop was to assess the applicability of an emerging repertoire of genomic technologies to studies of human germ-cell mutagenesis. Workshop participants recommended large-scale human germ-cell mutation studies be conducted using samples from donors with high-dose exposures, such as cancer survivors. Within this high-risk cohort, parents and children could be evaluated for heritable changes in (a) DNA sequence and chromosomal structure, (b) repeat sequences and minisatellites, and (c) global gene expression profiles and pathways. Participants also advocated the establishment of a bio-bank of human tissue samples from donors with well-characterized exposure, including medical and reproductive histories. This mutational resource could support large-scale, multipleendpoint studies. Additional studies could involve the examination of transgenerational effects NIH Public AccessAuthor Manuscript Environ Mol Mutagen. Author manuscript; available in PMC 2007 November 8. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript associated with changes in imprinting and methylation patterns, nucleotide repeats, and mitochondrial DNA mutations. The further development of animal models and the integration of these with human studies are necessary to provide molecular insights into the mechanisms of germcell mutations and to identify prevention strategies. Furthermore, scientific specialty groups should be convened to review and prioritize the evidence for germ-cell mutagenicity from common environmental, occupational, medical, and lifestyle exposures. Workshop attendees agreed on the need for a full-scale assault to address key fundamental questions in human germ-cell environmental mutagenesis. These include, but are not limited to, the following: Do human germ-cell mutagens exist? What are the risks to future generations? Are some parents at higher risk than others for acquiring and transmitting germ-cell mutations? Obtaining answers to these, and other critical questions, will require strong support from relevant funding agencies, in addition to the engagement of scientists outside the fields of genomics and germ-cell mutagenesis.

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Section: Bioinformatics Tools In Germ-cell Analysesmentioning

confidence: 99%

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Wyrobek

Mulvihill

Wassom

et al. 2007

Environ and Mol Mutagen

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“…1,2 In the last 25 years, advances in molecular biology and genomics have significantly improved our knowledge of spermatogenesis by identifying numerous genes essential for the process. [3][4][5][6] However, these transcriptomic databases do not provide crucial information on the post-transcriptional control of gene expression, changes in protein expression levels or protein modifications. Moreover, transcriptomics poses certain limitations as the expression levels of the majority of mRNAs and proteins are not always correlated.…”

Section: Introductionmentioning

confidence: 99%

Proteomics of spermatogenesis: from protein lists to understanding the regulation of male fertility and infertility

Huang¹,

Sha²

2010

Asian J Androl

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Proteomic technologies have undergone significant development in recent years, which has led to extensive advances in protein research. Currently, proteomic approaches have been applied to many scientific areas, including basic research, various disease and malignant tumour diagnostics, biomarker discovery and other therapeutic applications. In addition, proteomics-driven research articles examining reproductive biology and medicine are becoming increasingly common. The key challenge for this field is to move from lists of identified proteins to obtaining biological information regarding protein function. The present article reviews the available scientific literature related to spermatogenesis. In addition, this study uses two-dimensional electrophoresis mass spectrometry (2DE-MS) and liquid chromatography (LC)-MS to construct a series of proteome profiles describing spermatogenesis. This large-scale identification of proteins provides a rich resource for elucidating the mechanisms underlying male fertility and infertility.

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“…spermiogenesis), while other cell types are obtained at very low purity levels (18). Consequently, most differential gene expression studies on isolated spermatogenic cell populations are based on the comparison of transcripts specifically identified in P spermatocytes and RS (e.g., 24,33,34).…”

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confidence: 99%

High‐purity flow sorting of early meiocytes based on DNA analysis of guinea pig spermatogenic cells

et al. 2011

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Mammalian spermatogenesis is still nowadays poorly understood at the molecular level. Testis cellular heterogeneity is a major drawback for spermatogenic gene expression studies, especially when research is focused on stages that are usually very short and poorly represented at the cellular level such as initial meiotic prophase I (i.e., leptotene [L] and zygotene [Z]). Presumably, genes whose products are involved in critical meiotic events such as alignment, pairing and recombination of homologous chromosomes are expressed during the short stages of early meiotic prophase. Aiming to characterize mammalian early meiotic gene expression, we have found the guinea pig (Cavia porcellus) as an especially attractive model. A detailed analysis of its first spermatogenic wave by flow cytometry (FCM) and optical microscopy showed that guinea pig testes exhibit a higher representation of early meiotic stages compared to other studied rodents, partly because of their longer span, and also as a result of the increased number of cells entering meiosis. Moreover, we have found that adult guinea pig testes exhibit a peculiar 4C DNA content profile, with a bimodal peak for L/Z and P spermatocytes that is absent in other rodents. Besides, we show that this unusual 4C peak allows the separation by FCM of highly pure L/Z spermatocyte populations aside from pachytene ones, even from adult individuals. To our knowledge, this is the first report on an accurate and suitable method for highly pure early meiotic prophase cell isolation from adult mammals, and thus sets an interesting approach for gene expression studies aiming at a deeper understanding of the molecular groundwork underlying male gamete production. ' International Society for Advancement of CytometryKey terms meiosis; spermatogenesis; flow cytometry; cell sorting; guinea pig; meiotic prophase; gene expression SPERMATOGENESIS can be viewed as the simultaneous and coordinated execution of three individual programs of gene expression: somatic proliferation of spermatogonia, meiosis, and spermiogenesis (1). In the seminiferous tubules of adult mammals, germ cells in different maturation steps coexist, with C (round spermatids, elongating and elongated spermatids, spermatozoa), 2C (several types of G1 spermatogonia, secondary spermatocytes) and 4C (different stages of primary spermatocytes, G2 spermatogonia) DNA content. Moreover, somatic Sertoli cells (2C) coexist with germ cells inside the tubules, which are surrounded by peritubular myoid cells and immersed in a stroma containing fibroblasts, lymphocytes, mastocytes, macrophages, and Leydig cells (all of them 2C).Beside the obvious importance of spermatogenesis as a source of male reproductive cells, along the lengthy first meiotic prophase significant events such as the recognition, alignment, pairing (synapsis), and recombination (crossing over) of homologous chromosomes take place (2-5). Particularly, meiotic homologous recombination has vital importance for genetic variability (6). Furthermore, mutations of

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Expression Profiling of Mammalian Male Meiosis and Gametogenesis Identifies Novel Candidate Genes for Roles in the Regulation of Fertility

Cited by 119 publications

References 75 publications

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Proteomics of spermatogenesis: from protein lists to understanding the regulation of male fertility and infertility

High‐purity flow sorting of early meiocytes based on DNA analysis of guinea pig spermatogenic cells

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