Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy.
Humans
Pregnancy
Female
Diabetes, Gestational
/ genetics
Epigenesis, Genetic
/ genetics
Adult
DNA Methylation
/ genetics
Muscle, Skeletal
/ metabolism
Adolescent
Adipose Tissue
/ metabolism
Male
Prenatal Exposure Delayed Effects
/ genetics
Child
Diabetes Mellitus, Type 1
/ genetics
RNA, Untranslated
/ genetics
RNA, Long Noncoding
/ genetics
CpG Islands
/ genetics
Adipose
DNA methylation
Developmental programming
Epigenetics
Gene expression
Gestational diabetes
Intrauterine hyperglycemia
Muscle
Type 1 diabetes
VTRNA2-1
nc886
ncRNA
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
07 May 2024
07 May 2024
Historique:
received:
12
01
2024
accepted:
20
04
2024
medline:
8
5
2024
pubmed:
8
5
2024
entrez:
7
5
2024
Statut:
epublish
Résumé
Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. To identify DMRs, we employed the bump hunter method in samples from young (9-16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28-33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity. Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.
Sections du résumé
BACKGROUND
BACKGROUND
Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA.
METHODS
METHODS
To identify DMRs, we employed the bump hunter method in samples from young (9-16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28-33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle.
RESULTS
RESULTS
One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity.
CONCLUSIONS
CONCLUSIONS
Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.
Identifiants
pubmed: 38715048
doi: 10.1186/s13148-024-01673-3
pii: 10.1186/s13148-024-01673-3
doi:
Substances chimiques
RNA, Untranslated
0
RNA, Long Noncoding
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
61Subventions
Organisme : Novo Nordisk Fonden
ID : NNF17SA0031406
Organisme : Novo Nordisk Fonden
ID : NNF17SA0031406
Organisme : Novo Nordisk Fonden
ID : NNF17SA0031406
Organisme : Novo Nordisk Fonden
ID : NNF17SA0031406
Organisme : Novo Nordisk Fonden
ID : NNF17SA0031406
Organisme : Novo Nordisk Foundation Center for Basic Metabolic Research
ID : NNF18CC0034900
Organisme : Novo Nordisk Foundation Center for Basic Metabolic Research
ID : NNF18CC0034900
Organisme : The Innovation Fund Denmark
ID : 09-067124
Organisme : The Innovation Fund Denmark
ID : 09-067124
Organisme : The Innovation Fund Denmark
ID : 09-067124
Organisme : The Innovation Fund Denmark
ID : 09-067124
Organisme : The Innovation Fund Denmark
ID : 09-067124
Organisme : The Innovation Fund Denmark
ID : 09-067124
Organisme : The Innovation Fund Denmark
ID : 09-067124
Informations de copyright
© 2024. The Author(s).
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