Evidence map›Paper›PMID 40702545›Full record

ArticleClinical epigenetics2025

LINE-1 Methylation sustains telomere length in pregnant women: effects on pregnancy failure.

Donato Gemmati, Fabio Scarpellini, Francesca Salvatori, Elisabetta D'Aversa, Roberto Marci, Roberta Capucci, Bianca Antonica, Miriana Grisafi, Elisa Turato, Joanne Vanessa Vargas and 4 more

Abstract read
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

14 authors.

Donato GemmatiDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy. d.gemmati@unife.it.
Fabio ScarpelliniCentre for Reproductive Medicine, CERM Hungaria, 00193, Rome, Italy.
Francesca SalvatoriDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
Elisabetta D'AversaDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
Roberto MarciDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
Roberta CapucciDepartment of Medical Sciences, University of Ferrara, 44121, Ferrara, Italy.
Bianca AntonicaDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
Miriana GrisafiDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
Elisa TuratoDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
Joanne Vanessa VargasDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
Paola SecchieroDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
Giorgio ZauliDepartment of Environmental Sciences and Prevention, University of Ferrara, 44121, Ferrara, Italy.
Ajay V SinghDepartment of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), 10589, Berlin, Germany.
Veronica TisatoDepartment of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy. veronica.tisato@unife.it.

Funding

Local Ferrara University Grants FAR and FIRD
6 · The paper itself

Abstract

backgroundPregnancy loss is one of the most common adverse events during the first weeks of gestation, and the incidence increases with maternal age and in presence of selected risk factors. Nonetheless, no risk factors have been identified in most cases, considering these cases unexplained. Fertility rate decreases as maternal age increases and epigenetic age-dependent conditions may favor miscarriage. DNA methylation and telomere length are informative of aging and cell senescence, and their assessment has been evaluated as predictors of successful pregnancy.

resultsTelomere length (TL; T/S) and LINE-1 methylation (LINE-1; %) have been assessed in a cohort of 242 pregnant women by comparing spontaneous early miscarriage (EPL, n = 129) with voluntary interruption (VPI, n = 113). Telomere size and LINE-1 methylation rate drastically decreased as the age of women increased (P < 0.000001) with EPL group having lower values (T/S: 322.6 ± 142.0 versus 455.0 ± 290.6; P < 0.000001 and LINE-1 %: 81.66 ± 4.2 versus 86.01 ± 3.7; P < 0.000001) also characterized by stronger age-dependent lowering compared to VPI (P = 0.00035 and P < 0.000001, respectively). A global improvement in TL was observed as LINE-1 methylation rate increased, and it was more evident in EPL than in VPI (P < 0.000001). Focusing on the area below the 25th percentile of TL and LINE-1 % distribution, an overrepresentation of EPL cases was observed (P < 0.000001). On the contrary, VPI controls were dramatically overrepresented (P < 0.000001) in the area above the respective 75th percentiles. The mutual comparison of the number of EPL and VPI in these two extreme areas (EPL/VPI

conclusionsOverall, this suggests a combined effect of short telomeres and low methylation in phenotype worsening and a significant role of methylation in sustaining telomere size. These data support the hypothesis that different levels of DNA methylation may capture different biological mechanisms underlying telomere dynamics and dysfunctions and chromatin organization. Therefore, the concomitant assessment of telomere, methylation and their mutual interactions may be a novel strategy to translate the classical informative biomarkers of aging in the field of human reproduction.

Indexed as

Abortion, SpontaneousDNA MethylationLong Interspersed Nucleotide ElementsTelomereAdultEpigenesis, GeneticFemaleHumansMaternal AgePregnancyRisk FactorsTelomere HomeostasisYoung AdultAgingDNA-methylationEpigeneticsLINE-1Pregnancy lossTelomere length

Identifiers

PMID40702545
PMCPMC12288275

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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.