ArticleNature communications2023
Paternal methotrexate exposure affects sperm small RNA content and causes craniofacial defects in the offspring.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Parental autoimmune diseases and offspring's allergic disease: A systematic review and meta-analysis.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Pooled it
- Emerging roles of RNA N5-methylcytosine modification in reproductive physiology and gynecological diseases.Epigenetics · 2026Review
- Fertility and Birth Outcomes in Rheumatoid Arthritis: A Narrative Review.Rheumatology and therapy · 2026Review
- qMAP decodes RNA fragmentation dynamics in development and disease.Molecular systems biology · 2026Article
- Dissecting the small RNA code of inflammatory bowel disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- Optimized identification and characterization of small RNAs with PANDORA-seq.Nature protocols · 2025Review
- Epididymal dynamics and preimplantation roles of a sperm-enriched 5' fragment of tRNA-valine.Cell reports · 2025Article
- Parental preconceptual α-cypermethrin exposure alters embryonic brain transcriptomics in mice: Implications for autism spectrum disorder and stress vulnerability.Neurotoxicology · 2025Article
- Emerging roles of transfer RNA fragments in the CNS.Brain : a journal of neurology · 2025Review
- Sperm-borne small non-coding RNAs: potential functions and mechanisms as epigenetic carriers.Cell & bioscience · 2025Review
- Paternal hypercholesterolemia elicits sex-specific exacerbation of atherosclerosis in offspring.JCI insight · 2024Article
- Roles and regulation of tRNA-derived small RNAs in animals.Nature reviews. Molecular cell biology · 2024Review
- tRNA renovatio: Rebirth through fragmentation.Molecular cell · 2023Review
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 5 institutions in 3 countries.
Funding
Abstract
Folate is an essential vitamin for vertebrate embryo development. Methotrexate (MTX) is a folate antagonist that is widely prescribed for autoimmune diseases, blood and solid organ malignancies, and dermatologic diseases. Although it is highly contraindicated for pregnant women, because it is associated with an increased risk of multiple birth defects, the effect of paternal MTX exposure on their offspring has been largely unexplored. Here, we found MTX treatment of adult medaka male fish (Oryzias latipes) causes cranial cartilage defects in their offspring. Small non-coding RNA (sncRNAs) sequencing in the sperm of MTX treated males identify differential expression of a subset of tRNAs, with higher abundance for specific 5' tRNA halves. Sperm RNA methylation analysis on MTX treated males shows that m5C is the most abundant and differential modification found in RNAs ranging in size from 50 to 90 nucleotides, predominantly tRNAs, and that it correlates with greater testicular Dnmt2 methyltransferase expression. Injection of sperm small RNA fractions from MTX-treated males into normal fertilized eggs generated cranial cartilage defects in the offspring. Overall, our data suggest that paternal MTX exposure alters sperm sncRNAs expression and modifications that may contribute to developmental defects in their offspring.
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.