ArticleFertility and sterility2022
DNA comethylation analysis reveals a functional association between BRCA1 and sperm DNA fragmentation.
Article in Fertility and sterility, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Sperm DNA methylation profiling in patients with Kallmann syndrome.Endocrine connections · 2025Article
- Perspective in the Mechanisms for Repairing Sperm DNA Damage.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo identify the DNA comethylation patterns associated with sperm DNA fragmentation (SDF) and to explore the potential associations of hub genes with SDF.
designProspective study.
settingUniversity-affiliated reproductive medicine center. PATIENT(S): A total of 300 male patients consulting for couple infertility were recruited from the First Affiliated Hospital of Wenzhou Medical University. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Comethylation network analysis based on the genome-wide methylation profile of spermatozoal DNA from 20 men was performed to identify hub modules and genes involved in SDF. Human spermatozoa were used for targeted bisulfite amplicon sequencing (267 men) or droplet digital polymerase chain reaction (45 men). The potential role of Brca1 in DNA damage was explored in mouse GC2 spermatocyte cells. Oxidative damage to spermatocytes was modeled by incubating GC2 cells with H RESULT(S): BRCA1 was identified as a hub gene in SDF. Promoter hypermethylation of BRCA1 was observed in those samples with a high DNA fragmentation index (DFI) compared to those with a low DFI. Concomitantly, BRCA1 mRNA expression was lower in samples with a high DFI than with a low DFI. In the GC2 cell model, Brca1 knockdown reduced cell proliferation and increased sensitivity to oxidative stress. Moreover, it increased double-strand breaks and decreased the protein levels of the DNA repair genes MRE11 and RAD51. CONCLUSION(S): A prominent cluster of comethylated patterns associated with SDF was identified. BRCA1 may be the hub gene involved in sperm DNA damage.
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