RANKL regulates male reproductive function

Martin Blomberg Jensen (), Christine Hjorth Andreassen, Anne Jørgensen, John Erik Nielsen, Li Juel Mortensen, Ida Marie Boisen, Peter Schwarz, Jorma Toppari, Roland Baron, Beate Lanske and Anders Juul
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Martin Blomberg Jensen: Rigshospitalet, University of Copenhagen
Christine Hjorth Andreassen: Rigshospitalet, University of Copenhagen
Anne Jørgensen: University of Copenhagen
John Erik Nielsen: University of Copenhagen
Li Juel Mortensen: Rigshospitalet, University of Copenhagen
Ida Marie Boisen: Rigshospitalet, University of Copenhagen
Peter Schwarz: University of Copenhagen
Jorma Toppari: Turku University Hospital
Roland Baron: Harvard University
Beate Lanske: Harvard University
Anders Juul: University of Copenhagen

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22734-8

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DOI: 10.1038/s41467-021-22734-8

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