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Cited by 18Gestational Diabetes Research and ManagementBirth, Development, and HealthEpigenetics and DNA Methylation

From Mother to Child: Epigenetic Signatures of Hyperglycemia and Obesity during Pregnancy

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Franzago, Marica, Borrelli, Paola, Di Nicola, Marta, Cavallo, Pierluigi, D’Adamo, Ebe, Di Tizio, Luciano, Gazzolo, Diego, Stuppia, Liborio +1 more·2024·Nutrients
DOI 10.3390/nu16203502PMC PMC11510513
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Abstract

Background: In utero exposure to maternal hyperglycemia and obesity can trigger detrimental effects in the newborn through epigenetic programming. We aimed to assess the DNA methylation levels in the promoters of MC4R and LPL genes from maternal blood, placenta, and buccal swab samples collected in children born to mothers with and without obesity and Gestational Diabetes Mellitus (GDM). Methods: A total of 101 Caucasian mother–infant pairs were included in this study. Sociodemographic characteristics, clinical parameters, physical activity, and adherence to the Mediterranean diet were evaluated in the third trimester of pregnancy. Clinical parameters of the newborns were recorded at birth. Results: A negative relationship between MC4R DNA methylation on the fetal side of the GDM placenta and birth weight (r = −0.630, p = 0.011) of newborns was found. MC4R DNA methylation level was lower in newborns of GDM women (CpG1: 2.8% ± 3.0%, CpG2: 3.8% ± 3.3%) as compared to those of mothers without GDM (CpG1: 6.9% ± 6.2%, CpG2: 6.8% ± 5.6%; p < 0.001 and p = 0.0033, respectively), and it was negatively correlated with weight (r = −0.229; p = 0.035), head circumference (r = −0.236; p = 0.030), and length (r = −0.240; p = 0.027) at birth. LPL DNA methylation was higher on the fetal side of the placenta in obese patients as compared to normal-weight patients (66.0% ± 14.4% vs. 55.7% ± 15.2%, p = 0.037), and it was associated with maternal total cholesterol (r = 0.770, p = 0.015) and LDL-c (r = 0.783, p = 0.012). Conclusions: These results support the role of maternal MC4R and LPL methylation in fetal programming and in the future metabolic health of children.

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References 46 · Cited by 18

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Authors
Franzago, M., Borrelli, P., Di Nicola, M., Cavallo, P., D’Adamo, E., Di Tizio, L., Gazzolo, D., Stuppia, L., & Vitacolonna, E.
Affiliations
  • University of Chieti-Pescara (IT)
  • Laboratory of Biostatistics, Department of Medical, Oral and Biotechnological Sciences, “G. D’Annunzio” University, Chieti-Pescara, 66100 Chieti, Italy
  • Department of Obstetrics and Gynaecology, SS. Annunziata Hospital, “G. D’Annunzio” University, 66100 Chieti, Italy
Corresponding author
Vitacolonna, Ester
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2024-10-16
Volume
16
Issue
20
Pages
3502
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu16203502
PMC
PMC11510513
OpenAlex
W4403611317
Cited by
18
References
46
Citations by year
2026: 6 · 2025: 11 · 2024: 1
FWCI
9.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Italian Ministry of Health (D73C22001670006)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
maternal hyperglycemia, maternal obesity, gestational diabetes mellitus, epigenetic programming, DNA methylation, melanocortin-4 receptor, lipoprotein lipase, placenta, newborn birth weight, fetal programming, maternal blood, buccal swabs, Mediterranean diet, LDL cholesterol
MeSH terms
Adult, Birth Weight, Female, Humans, Hyperglycemia, Infant, Newborn, Lipoprotein Lipase, Male, Obesity, Placenta, Pregnancy, Prenatal Exposure Delayed Effects, Promoter Regions, Genetic, Diabetes, Gestational, DNA Methylation, Receptor, Melanocortin, Type 4, Epigenesis, Genetic

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