ArticlePloS one2012
Selfish spermatogonial selection: evidence from an immunohistochemical screen in testes of elderly men.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: IV: Current and Future Utilization of Molecular-Genetic Tests for Testicular Germ Cell Tumors.The American journal of surgical pathology · 2020Guideline
- Effects of Aging on Mammalian Spermatogenesis From a Cellular Perspective.Molecular reproduction and development · 2025Review
- Germline mosaicism in TCF20-associated neurodevelopmental disorders: a case study and literature review.Journal of human genetics · 2025Review
- Direct measurement of the male germline mutation rate in individuals using sequential sperm samples.Nature communications · 2025Article
- Human embryonic genetic mosaicism and its effects on development and disease.Nature reviews. Genetics · 2024Review
- New perspectives on fertility in transwomen with regard to spermatogonial stem cells.Reproduction & fertility · 2023Review
- Non-neutral clonal selection and its potential role in mammalian germline stem cell dysfunction with advancing age.Frontiers in cell and developmental biology · 2022Review
- A six-attribute classification of genetic mosaicism.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Review
- Excessive unilateral proliferation of spermatogonia in a patient with non-obstructive azoospermia - adverse effect of clomiphene citrate pre-treatment?Basic and clinical andrology · 2020Article
- Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations.Orphanet journal of rare diseases · 2019Article
- Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology.International journal of molecular sciences · 2019Review
- Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes.Genome research · 2018Article
- Testicular cancer.Nature reviews. Disease primers · 2018Review
- Genomic mosaicism in paternal sperm and multiple parental tissues in a Dravet syndrome cohort.Scientific reports · 2017Article
- Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development.Cell stem cell · 2017Article
- Spermatogonial Stem Cells: Implications for Genetic Disorders and Prevention.Stem cells and development · 2016Article
- Germline Stem Cell Competition, Mutation Hot Spots, Genetic Disorders, and Older Fathers.Annual review of genomics and human genetics · 2016Review
- Cellular correlates of selfish spermatogonial selection.Andrology · 2016Article
- Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Contributions of intrinsic mutation rate and selfish selection to levels of de novo HRAS mutations in the paternal germline.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The dominant congenital disorders Apert syndrome, achondroplasia and multiple endocrine neoplasia-caused by specific missense mutations in the FGFR2, FGFR3 and RET proteins respectively-represent classical examples of paternal age-effect mutation, a class that arises at particularly high frequencies in the sperm of older men. Previous analyses of DNA from randomly selected cadaveric testes showed that the levels of the corresponding FGFR2, FGFR3 and RET mutations exhibit very uneven spatial distributions, with localised hotspots surrounded by large mutation-negative areas. These studies imply that normal testes are mosaic for clusters of mutant cells: these clusters are predicted to have altered growth and signalling properties leading to their clonal expansion (selfish spermatogonial selection), but DNA extraction eliminates the possibility to study such processes at a tissue level. Using a panel of antibodies optimised for the detection of spermatocytic seminoma, a rare tumour of spermatogonial origin, we demonstrate that putative clonal events are frequent within normal testes of elderly men (mean age: 73.3 yrs) and can be classed into two broad categories. We found numerous small (less than 200 cells) cellular aggregations with distinct immunohistochemical characteristics, localised to a portion of the seminiferous tubule, which are of uncertain significance. However more infrequently we identified additional regions where entire seminiferous tubules had a circumferentially altered immunohistochemical appearance that extended through multiple serial sections that were physically contiguous (up to 1 mm in length), and exhibited enhanced staining for antibodies both to FGFR3 and a marker of downstream signal activation, pAKT. These findings support the concept that populations of spermatogonia in individual seminiferous tubules in the testes of older men are clonal mosaics with regard to their signalling properties and activation, thus fulfilling one of the specific predictions of selfish spermatogonial selection.
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.