ArticleScientific reports2021
Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.Aging cell · 2024Pooled it
- Fertility in the aging male: a systematic review.Fertility and sterility · 2022Pooled it
- Adipose-Derived Mesenchymal Stem Cells Alleviate ᴅ-Galactose-Induced Testicular Injury by Activating the Keap1/Nrf2 Pathway and Suppressing NLRP3-Associated Pyroptosis.Antioxidants (Basel, Switzerland) · 2026Article
- Integrated single-nucleus transcriptomic and chromatin accessibility analysis reveals key molecular basis of human testicular aging.Journal of molecular cell biology · 2026Article
- Review
- Associations Between Perceived Stress and Sperm DNA Methylation Among Men Attending a Fertility Center.Andrology · 2026Article
- Article
- Clinical Implications of Paternal Age in Assisted Reproduction: Integrating Sperm Epigenetic Evidence.Journal of clinical medicine · 2026Review
- Article
- Article
- Epigenetic effects of Qixiong Formula on sperm DNA methylation in a rat model of asthenozoospermia.Translational andrology and urology · 2025Article
- Embryonic signatures of intergenerational epigenetic inheritance across paternal environments and genetic backgrounds.The EMBO journal · 2025Article
- Sperm rDNA Copy Number and Methylation Are Associated with Male-Factor Infertility.International journal of molecular sciences · 2025Article
- Epigenetic links between paternal age, reproduction, and offspring health: a focus on sncRNAs.Reproduction & fertility · 2025Review
- Toward predictive andrology: integrating basic semen analysis mitochondrial deoxyribonucleic acid and artificial intelligence to forecast reproductive outcomes.F&S reports · 2025Article
- Beyond Genes: Mechanistic and Epidemiological Insights into Paternal Environmental Influence on Offspring Health.Current environmental health reports · 2025Review
- Whole-genome bisulfite sequencing of X and Y sperm in Holstein bulls reveals differences in autosomal methylation status.BMC genomics · 2025Article
- Observational
- Introducing artificial intelligence and sperm epigenetics in the fertility clinic: a novel foundation for diagnostics and prediction modelling.Frontiers in reproductive health · 2025Article
- Tackling somatic DNA contamination in sperm epigenetic studies.Frontiers in reproductive health · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Parental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in sperm DNA methylation over time is one potential explanation. We assessed genome-wide methylation of sperm DNA from 47 semen samples collected from male participants of couples seeking infertility treatment. We report that higher male age was associated with lower likelihood of fertilization and live birth, and poor embryo development (p < 0.05). Furthermore, our multivariable linear models showed male age was associated with alterations in sperm methylation at 1698 CpGs and 1146 regions (q < 0.05), which were associated with > 750 genes enriched in embryonic development, behavior and neurodevelopment among others. High dimensional mediation analyses identified four genes (DEFB126, TPI1P3, PLCH2 and DLGAP2) with age-related sperm differential methylation that accounted for 64% (95% CI 0.42-0.86%; p < 0.05) of the effect of male age on lower fertilization rate. Our findings from this modest IVF population provide evidence for sperm methylation as a mechanism of age-induced poor reproductive outcomes and identifies possible candidate genes for mediating these effects.
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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.