DNA Methylation Signatures in Paired Placenta and Umbilical Cord Samples: Relationship with Maternal Pregestational Body Mass Index and Offspring Metabolic Outcomes
Ariadna Gómez-Vilarrubla,
Berta Mas-Parés,
Gemma Carreras-Badosa,
Alexandra Bonmatí-Santané,
Jose-Maria Martínez-Calcerrada,
Maria Niubó-Pallàs,
Francis de Zegher,
Lourdes Ibáñez,
Abel López-Bermejo,
Judit Bassols
Affiliations
Ariadna Gómez-Vilarrubla
Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain
Berta Mas-Parés
Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain
Gemma Carreras-Badosa
Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain
Alexandra Bonmatí-Santané
Department of Gynecology, Dr. Josep Trueta Hospital, 17007 Girona, Spain
Jose-Maria Martínez-Calcerrada
Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain
Maria Niubó-Pallàs
Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain
Francis de Zegher
Department of Development & Regeneration, University of Leuven, 3000 Leuven, Belgium
Lourdes Ibáñez
Endocrinology, Pediatric Research Institute, Sant Joan de Déu Children’s Hospital, 08950 Esplugues de Llobregat, Spain
Abel López-Bermejo
Pediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain
Judit Bassols
Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), 17190 Salt, Spain
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.