RANKL regulates male reproductive function
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RANKL regulates male reproductive function. / Blomberg Jensen, Martin; Andreassen, Christine Hjorth; Jørgensen, Anne; Nielsen, John Erik; Juel Mortensen, Li; Boisen, Ida Marie; Schwarz, Peter; Toppari, Jorma; Baron, Roland; Lanske, Beate; Juul, Anders.
I: Nature Communications, Bind 12, Nr. 1, 2450, 12.2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - RANKL regulates male reproductive function
AU - Blomberg Jensen, Martin
AU - Andreassen, Christine Hjorth
AU - Jørgensen, Anne
AU - Nielsen, John Erik
AU - Juel Mortensen, Li
AU - Boisen, Ida Marie
AU - Schwarz, Peter
AU - Toppari, Jorma
AU - Baron, Roland
AU - Lanske, Beate
AU - Juul, Anders
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-021-22734-8
DO - 10.1038/s41467-021-22734-8
M3 - Journal article
C2 - 33893301
AN - SCOPUS:85104855063
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2450
ER -
ID: 286313377