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Integration and reanalysis of transcriptomics and methylomics data derived from blood and testis tissue of men with 47,XXY Klinefelter syndrome indicates the primary involvement of Sertoli cells in the testicular pathogenesis

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DOI

  1. Minipuberty in Klinefelter syndrome: Current status and future directions

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. 47,XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Mutation-based growth charts for SEDC and other COL2A1 related dysplasias

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Activin A determines steroid levels and composition in the fetal testis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours

    Research output: Contribution to journalReviewResearchpeer-review

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Klinefelter syndrome (KS; 47,XXY) is the most common sex chromosomal anomaly and causes a multitude of symptoms. Often the most noticeable symptom is infertility caused by azoospermia with testicular histology showing hyalinization of tubules, germ cells loss, and Leydig cell hyperplasia. The germ cell loss begins early in life leading to partial hyalinization of the testis at puberty, but the mechanistic drivers behind this remain poorly understood. In this systematic review, we summarize the current knowledge on developmental changes in the cellularity of KS gonads supplemented by a comparative analysis of the fetal and adult gonadal transcriptome, and blood transcriptome and methylome of men with KS. We identified a high fraction of upregulated genes that escape X-chromosome inactivation, thus supporting previous hypotheses that these are the main drivers of the testicular phenotype in KS. Enrichment analysis showed overrepresentation of genes from the X- and Y-chromosome and testicular transcription factors. Furthermore, by re-evaluation of recent single cell RNA-sequencing data originating from adult KS testis, we found novel evidence that the Sertoli cell is the most affected cell type. Our results are consistent with disturbed cross-talk between somatic and germ cells in the KS testis, and with X-escapee genes acting as mediators.

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Volume184
Issue number2
Pages (from-to)239-255
Number of pages17
ISSN1552-4868
DOIs
Publication statusPublished - Jun 2020

    Research areas

  • human testis, Klinefelter syndrome, methylome, single cell RNA-sequencing, transcriptome

ID: 59984037