Evidence map›Paper›PMID 33661909›Full record

ArticlePLoS genetics2021

Stability of the cytosine methylome during post-testicular sperm maturation in mouse.

Carolina Galan, Ryan W Serra, Fengyun Sun, Vera D Rinaldi, Colin C Conine, Oliver J Rando

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 36 citations in OpenAlex.

  1. On the state of chromatin in mammalian sperm.bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Article
  4. Characteristic analysis of NBMC genomics · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. QTLs and Candidate Genes Associated with Semen Traits in Merino Sheep.Animals : an open access journal from MDPI · 2023
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Carolina GalanDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0001-9557-6034
Ryan W SerraDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0001-8037-0666
Fengyun SunDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Vera D RinaldiDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0002-0051-1754
Colin C ConineDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0001-7915-0463
Oliver J RandoDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0003-1516-9397
University of Massachusetts Chan Medical School · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3M
Dietary effects on the sperm epigenomeR01HD080224 · NICHD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RANDO, OLIVER J · 2014 to 2022
$5.9M
Replication-independent DNA methylation dynamics during post-testicular sperm maturationF31HD097928 · NICHD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GALAN, CAROLINA · 2019 to 2021
$65k
NICHD NIH HHS F31 HD097928NICHD NIH HHS R01 HD080224NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

Beyond the haploid genome, mammalian sperm carry a payload of epigenetic information with the potential to modulate offspring phenotypes. Recent studies show that the small RNA repertoire of sperm is remodeled during post-testicular maturation in the epididymis. Epididymal maturation has also been linked to changes in the sperm methylome, suggesting that the epididymis might play a broader role in shaping the sperm epigenome. Here, we characterize the genome-wide methylation landscape in seven germ cell populations from throughout the male reproductive tract. We find very few changes in the cytosine methylation landscape between testicular germ cell populations and cauda epididymal sperm, demonstrating that the sperm methylome is stable throughout post-testicular maturation. Although our sequencing data suggested that caput epididymal sperm exhibit a highly unusual methylome, follow-up studies revealed that this resulted from contamination of caput sperm by extracellular DNA. Extracellular DNA formed web-like structures that ensnared sperm, and was present only in sperm samples obtained from the caput epididymis and vas deferens of virgin males. Curiously, contaminating extracellular DNA was associated with citrullinated histone H3, potentially resulting from a PAD-driven genome decondensation process. Taken together, our data emphasize the stability of cytosine methylation in mammalian sperm, and identify a surprising, albeit transient, period during which sperm are associated with extracellular DNA.

Indexed as

DNA MethylationEpigenomeAnimalsCell DifferentiationCell-Free Nucleic AcidsCpG IslandsCytosineEpididymisFemaleMaleMiceSpermatozoaSperm MaturationTestisCell-Free Nucleic AcidsCytosine

Identifiers

PMID33661909
PMCPMC7963034
OpenAlexW3133903516

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.