Evidence map›Paper›PMID 38172913›Full record

ArticleClinical epigenetics2024

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence.

Ivona Bečeheli, Marina Horvatiček, Maja Perić, Barbara Nikolić, Cyrielle Holuka, Marija Klasić, Marina Ivanišević, Mirta Starčević, Gernot Desoye, Dubravka Hranilović and 2 more

Open access · goldAbstract read
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Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.5field-weighted citation impact, top 8% 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

8 citing papers in PubMed, 6 citations in OpenAlex.

  1. Beyond Deterministic Fetal Programming: Intrauterine Exposures and the Multifactorial Origins of Adiposity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026
    Review
  2. A Review of the Effects of Maternal and Paternal Obesity on Neurodevelopmental Disorders and Related Neurobiology in Rodent and Human Offspring.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026
    Review
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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

12 authors at 6 institutions in 3 countries.

Ivona BečeheliDivision of Molecular Biology, Ruđer Bošković Institute, 10000, Zagreb, Croatia.
Marina HorvatičekDivision of Molecular Biology, Ruđer Bošković Institute, 10000, Zagreb, Croatia.
Maja PerićDivision of Molecular Biology, Ruđer Bošković Institute, 10000, Zagreb, Croatia.
Barbara NikolićDepartment of Biology, Faculty of Science, University of Zagreb, 10000, Zagreb, Croatia.
Cyrielle HolukaDepartment of Infection and Immunity, Luxembourg Institute of Health, 4354, Esch-sur-Alzette, Luxembourg.
Marija KlasićDepartment of Biology, Faculty of Science, University of Zagreb, 10000, Zagreb, Croatia.
Marina IvaniševićDepartment of Obstetrics and Gynecology, University Hospital Centre Zagreb, 10000, Zagreb, Croatia.
Mirta StarčevićDepartment of Neonatology, University Hospital Centre Zagreb, 10000, Zagreb, Croatia.
Gernot DesoyeDepartment of Obstetrics and Gynecology, Medical University of Graz, 8036, Graz, Austria.
Dubravka HranilovićDepartment of Biology, Faculty of Science, University of Zagreb, 10000, Zagreb, Croatia.
Jonathan D TurnerDepartment of Infection and Immunity, Luxembourg Institute of Health, 4354, Esch-sur-Alzette, Luxembourg.
Jasminka ŠtefuljDivision of Molecular Biology, Ruđer Bošković Institute, 10000, Zagreb, Croatia. jasminka.stefulj@irb.hr.
Rudjer Boskovic Institute · HRUniversity of Zagreb · HRUniversity Hospital Centre Zagreb · HRLuxembourg Institute of Health · LUMedical University of Graz · ATUniversity of Luxembourg · LU

Funding

COST Action CA18211Croatian Science Foundation DOK-2018-09-7794Croatian Science Foundation IP-2018-01-6547Fonds National de la Recherche (FNR) Luxembourg C19/SC/13650569 'ALAC'Ruđer Bošković Institute mobility grant no. 01-4070/4-2022.pm
6 · The paper itself

Abstract

backgroundSerotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters-pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)-and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database.

resultsNone of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites.

conclusionsMethylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

Indexed as

Diabetes, GestationalDNA MethylationAdolescentBlood CellsCesarean SectionFemaleFetal BloodGlucoseHumansInfant, NewbornMalePregnancySerotoninSerotonin Plasma Membrane Transport ProteinsGlucoseSerotoninSerotonin Plasma Membrane Transport ProteinsSLC6A4 protein, human5-HTALSPACDoHADEarly-life adversityEpigeneticMaternal obesitySex differences

Identifiers

PMID38172913
PMCPMC10765867
OpenAlexW4390571274

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LicenceCC BY
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Registered trials

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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.