ArticleNature communications2021
RANKL regulates male reproductive function.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of a Single-dose Denosumab on Semen Quality in Infertile Men (FITMI): A Randomized Controlled Trial
Novel Approach for Oligospermia (NAPO): A Randomized Controlled Trial
Novel Treatment of Some Men With Non-Obstructive Azoospermia (NT-NOA): A Clinical Interventional Study
Who cites it
20 citing papers in PubMed, 58 citations in OpenAlex.
- Effects of a single-dose denosumab on glucose and lipid homeostasis in young infertile men.Endocrine · 2026Trial
- Effect of a single-dose denosumab on mineral homeostasis in infertile men: insights from a pilot intervention study and a randomized controlled trial.BMC medicine · 2025Trial
- Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity.Cell reports. Medicine · 2024Trial
- Low serum anti-Müllerian hormone is associated with semen quality in infertile men and not influenced by vitamin D supplementation.BMC medicine · 2023Trial
- Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis.Science (New York, N.Y.) · 2026Article
- Paternal Sertoli cell-derived extracellular vesicles transfer mtDNA and microRNA cargo to trigger germ cell oxidative stress and induce metabolic risks in offspring.Cell communication and signaling : CCS · 2026Article
- Melatonin mitigates methamphetamine-induced testicular oxidative stress, hormonal imbalance and seminiferous tubule degeneration in rats.BMC pharmacology & toxicology · 2026Article
- Characterisation of phosphate transport in epididymis and prostate with possible relevance for semen quality.EBioMedicine · 2025Article
- A comprehensive analysis of Atlantic salmon gonad and pituitary transcriptomes identifies novel players in sexual maturation.BMC genomics · 2025Article
- Transcriptional Changes in Cumulus Cells During In Vitro Maturation of Human Oocytes.Molecular reproduction and development · 2025Article
- Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction.Cell communication and signaling : CCS · 2025Article
- Novel approach for oligospermia (NAPO) - Protocol for a randomized controlled trial.Contemporary clinical trials communications · 2024Article
- High incidence of imperforate vagina in ADGRA3-deficient mice.BMC biology · 2024Article
- Special Staining and Protein Expression of VEGF/EGFR and P53/NF-κB in Cryptorchid Tissue of Erhualian Pigs.Life (Basel, Switzerland) · 2024Article
- Recent Progress of In Vitro 3D Culture of Male Germ Stem Cells.Journal of functional biomaterials · 2023Review
- Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study.Journal of clinical medicine · 2023Article
- Article
- Roles of osteoprotegerin in endocrine and metabolic disorders through receptor activator of nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B signaling.Frontiers in cell and developmental biology · 2022Review
- TNFAIP3 Reduction-of-Function Drives Female Infertility and CNS Inflammation.Frontiers in immunology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.