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Bringing epigenetics into the diagnostics of the andrology laboratory： challenges and perspectives

Asian Journal of Andrology 2014年第5期16卷 669-674,I0006页

作者： Ruth Klaver jorg gromoll Centre of Reproductive Medicine and Andrology University Clinics of MOnster MOnster Germany

Recent studies have shown significant associations of aberrant DNA methylation in spermatozoa with idiopathic male infertility, increased frequency of spontaneous abortions and imprinting disorders. Thus, the analysis of DNA methylation of specific genes in spermatozoa has the potential to become a new valuable diagnostic marker in clinical andrology. This perspective article discusses the current state and value of DNA methylation analysis in the diagnostic setup of infertile men and outlines challenges and perspectives. It highlights the potential of DNA methylation in andrological diagnostics and its putative benefit in the examination of hitherto idiopathic infertile patients is described.

关键词： DNA methylation male infertility spermatogenesis

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Epidermal growth factor receptor pathway substrate 8 (Eps8) expression in maturing testis

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Asian Journal of Andrology 2004年第3期6卷 195-203页

作者： Alain Wunsch Kai Strothmann Manuela Simoni jorg gromoll Eberhard Nieschlag C.Marc Luetjens Institute of Reproductive Medicine of the University D-48129 MunsterGermanyInstitute of Reproductive Medicine of the UniversityD-48129 MunsterGermanyInstitute of Reproductive Medicine of the UniversityD-48129 MunsterGermanyInstitute of Reproductive Medicine of the UniversityD-48129 MunsterGermanyInstitute of Reproductive Medicine of the UniversityD-48129 MunsterGermanyInstitute of Reproductive Medicine of the UniversityD-48129 MunsterGermany

Aim: Although epidermal growth factor receptors are expressed in the testes, whether they signal through epidermal growth factor receptor pathway substrate 8 (Eps8) is unknown. Here we evaluated the expression pattern of Eps8 in the maturing testis. Methods: The expression of Eps8 was analysed by Northern blotting, immunocy-tochemistry and Western blotting in primary Sertoli cell cultures and in testicular tissue of rodents. Results: Eps8 is specifically expressed in gonocytes, Leydig and Sertoli cells of the neonatal rats and in Leydig and Sertoli cells of the adult rats and mice. Although gonocytes express Eps8, no signal was found in prepubertal or mature spermatogonia and the expression level of Eps8 in Sertoli cells increases with age. No regulation of Eps8 expression in primary immature rat Sertoli cells by Follicle stimulating hormone (FSH) was detected by Western blotting. Conclusion: Eps8 seems to be involved in the growth factor-controlled regulation of cell proliferation and differentiation in the seminiferous epithelium. Eps8 is a possible marker for gonocytes and in Sertoli cells it could be involved in crosstalk with other growth factor pathways.

关键词： gene expression isoform Sertoli cell gonocyte

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Analysis of the genetic interactions between Cyclin A1, Atm and p53 during spermatogenesis

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Asian Journal of Andrology 2007年第6期9卷 739-750页

作者： Nicole Baiumer Marie-Luise Sandstede Sven Diederichs Gabriele Kohler Carol Readhead Ping Ji Feng Zhang Etmar Bulk jorg gromoll Wolfgang E. Berdel Hubert Serve Carsten Muller-Tidow Department of Medicine Hematology and Oncology University of Munster Domagstrasse 3 Munster 48149 Germany Department of Pathology University of Munster Domagstrasse 17 Munster 48149 Germany California Institute of Technology 1200 East California Boulevard Pasadena California 91125 USA Interdisciplinary Center for Clinical Research University of Munster Domagstrasse 3 Munster 48149 Germany Institute of Reproductive Medicine University of Munster Domagstrasse 12 Munster 48129 Germany

Aim： To analyze the functional interactions of Cyclin with p53 and Atm in spermatogenesis and DNA double- strand break repair. Methods： Two lines of double knockout mice were generated. Spermatogenesis and double strand break repair mechanisms were analyzed in Cyclin A1 （Ccnal）; p53- and Ccnal; Atm-double knockout mice. Results： The block in spermatogenesis observed in Cyclin A1-/- （Ccnal-/-） testes at the mid-diplotene stage is associated with polynucleated giant cells. We found that Ccnal-deficient testes and especially the giant cells accumulate unrepaired DNA double-strand breaks, as detected by immunohistochemistry for phosphorylated H2AX. In addition, the giant cells escape from apoptosis. The development of giant cells occurred in meiotic prophase I, because testes lacking ATM, which are known to develop spermatogenic arrest earlier than prophase I, do not develop giant cells in the absence of cyclin A1. Cyclin A1 interacted with p53 and phosphorylated p53 in complex with CDK2. Interestingly, p53-deficiency significantly increased the number of giant cells in Ccnal-deficient testes. Gene expression analyses of a panel of DNA repair genes in the mutant testes revealed that none of the genes examined were consistently misregulated in the absence of cyclin A1. Conclusion： Ccnal-deficiency in spermatogenesis is associated with defects in DNA double-strand break repair, which is enhanced by loss of p53.

关键词： spermatogenesis testis cell cycle meiosis DNA double-strand break giant cell knockout mice

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