Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

RANKL regulates male reproductive function

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Ultraviolet radiation drives mutations in a subset of mucosal melanomas

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Quantitative single-cell proteomics as a tool to characterize cellular hierarchies

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Thyroid function in COVID-19 and the association with cytokine levels and mortality

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The effects of selected inhibitors on human fetal adrenal steroidogenesis differs under basal and ACTH-stimulated conditions

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Cohort profile: The COPENHAGEN Minipuberty Study-A longitudinal prospective cohort of healthy full-term infants and their parents

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Infertile men have few treatment options. Here, we demonstrate that the transmembrane receptor activator of NF-kB ligand (RANKL) signaling system is active in mouse and human testis. RANKL is highly expressed in Sertoli cells and signals through RANK, expressed in most germ cells, whereas the RANKL-inhibitor osteoprotegerin (OPG) is expressed in germ and peritubular cells. OPG treatment increases wild-type mouse sperm counts, and mice with global or Sertoli-specific genetic suppression of Rankl have increased male fertility and sperm counts. Moreover, RANKL levels in seminal fluid are high and distinguishes normal from infertile men with higher specificity than total sperm count. In infertile men, one dose of Denosumab decreases RANKL seminal fluid concentration and increases serum Inhibin-B and anti-Müllerian-hormone levels, but semen quality only in a subgroup. This translational study suggests that RANKL is a regulator of male reproductive function, however, predictive biomarkers for treatment-outcome requires further investigation in placebo-controlled studies.

Original languageEnglish
Article number2450
JournalNature Communications
Volume12
Issue number1
Pages (from-to)2450
ISSN2041-1723
DOIs
Publication statusPublished - 23 Apr 2021

    Research areas

  • Animals, Anti-Mullerian Hormone/blood, Denosumab/pharmacology, Fertility/drug effects, Humans, Inhibins/antagonists & inhibitors, Male, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Osteoprotegerin/pharmacology, RANK Ligand/antagonists & inhibitors, Semen/drug effects, Semen Analysis/methods, Sertoli Cells/drug effects, Sperm Count, Spermatozoa/cytology

ID: 66477822