Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis

Research output: Contribution to journalJournal articleResearchpeer-review

  1. ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Single mRNP Analysis Reveals that Small Cytoplasmic mRNP Granules Represent mRNA Singletons

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Gamma-Aminobutyric Acid Signaling in Brown Adipose Tissue Promotes Systemic Metabolic Derangement in Obesity

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Differences in Cell Cycle Status Underlie Transcriptional Heterogeneity in the HSC Compartment

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Evaluation of Serum Insulin-like Factor 3 Quantification by LC-MS/MS as a Biomarker of Leydig Cell Function

    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. Use of stored serum in the study of time trends and geographical differences in exposure of pregnant women to phthalates

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Disruption of human fetal testis development is widely accepted to underlie testicular germ cell cancer (TGCC) origin and additional disorders within testicular dysgenesis syndrome (TDS). However, the mechanisms for the development of testicular dysgenesis in humans are unclear. We used ex vivo culture and xenograft approaches to investigate the importance of Nodal and Activin signaling in human fetal testis development. Inhibition of Nodal, and to some extent Activin, signaling disrupted seminiferous cord formation, abolished AMH expression, reduced androgen secretion, and decreased gonocyte numbers. Subsequent xenografting of testicular tissue rescued the disruptive effects on seminiferous cords and somatic cells but not germ cell effects. Stimulation of Nodal signaling increased the number of germ cells expressing pluripotency factors, and these persisted after xenografting. Our findings suggest a key role for Nodal signaling in the regulation of gonocyte differentiation and early human testis development with implications for the understanding of TGCC and TDS origin.

Original languageEnglish
JournalCell Reports
Volume25
Issue number7
Pages (from-to)1924-1937.e4
DOIs
Publication statusPublished - 13 Nov 2018

ID: 55630657