DNA Methylation Signatures in Paired Placenta and Umbilical Cord Samples: Relationship with Maternal Pregestational Body Mass Index and Offspring Metabolic Outcomes

Author:

Gómez-Vilarrubla Ariadna1ORCID,Mas-Parés Berta2ORCID,Carreras-Badosa Gemma2,Bonmatí-Santané Alexandra3,Martínez-Calcerrada Jose-Maria1,Niubó-Pallàs Maria1,de Zegher Francis4,Ibáñez Lourdes56ORCID,López-Bermejo Abel27,Bassols Judit1ORCID

Affiliation:

1. Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain

2. Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain

3. Department of Gynecology, Dr. Josep Trueta Hospital, 17007 Girona, Spain

4. Department of Development & Regeneration, University of Leuven, 3000 Leuven, Belgium

5. Endocrinology, Pediatric Research Institute, Sant Joan de Déu Children’s Hospital, 08950 Esplugues de Llobregat, Spain

6. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Health Institute Carlos III (ISCIII), 28029 Madrid, Spain

7. Department of Pediatrics, Dr. Josep Trueta Hospital, 17007 Girona, Spain

Abstract

An epigenomic approach was used to study the impact of maternal pregestational body mass index (BMI) on the placenta and umbilical cord methylomes and their potential effect on the offspring’s metabolic phenotype. DNA methylome was assessed in 24 paired placenta and umbilical cord samples. The differentially methylated CpGs associated with maternal pregestational BMI were identified and the metabolic pathways and the potentially related diseases affected by their annotated genes were determined. Two top differentially methylated CpGs were studied in 90 additional samples and the relationship with the offspring’s metabolic phenotype was determined. The results showed that maternal pregestational BMI is associated with the methylation of genes involved in endocrine and developmental pathways with potential effects on type 2 diabetes and obesity. The methylation and expression of HADHA and SLC2A8 genes in placenta and umbilical cord were related to several metabolic parameters in the offspring at 6 years (weight SDS, height SDS, BMI SDS, Δ BW-BMI SDS, FM SDS, waist, SBP, TG, HOMA-IR, perirenal fat; all p < 0.05). Our data suggest that epigenetic analysis in placenta and umbilical cord may be useful for identifying individual vulnerability to later metabolic diseases.

Funder

Instituto de Salud Carlos III

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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