Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy
(2024) In Clinical Epigenetics 16(1).- Abstract
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: To identify DMRs, we employed... (More)
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: 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: 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: 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.
(Less)
- author
- organization
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adipose, Developmental programming, DNA methylation, Epigenetics, Gene expression, Gestational diabetes, Intrauterine hyperglycemia, Muscle, nc886, ncRNA, Type 1 diabetes, VTRNA2-1
- in
- Clinical Epigenetics
- volume
- 16
- issue
- 1
- article number
- 61
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85192240327
- pmid:38715048
- ISSN
- 1868-7075
- DOI
- 10.1186/s13148-024-01673-3
- language
- English
- LU publication?
- yes
- id
- 8d9b51ad-c155-46ad-8d2b-914ac89eded3
- date added to LUP
- 2024-05-20 12:35:38
- date last changed
- 2024-05-21 03:00:03
@article{8d9b51ad-c155-46ad-8d2b-914ac89eded3,
abstract = {{<p>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: 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: 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: 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.</p>}},
author = {{Hjort, Line and Bredgaard, Sandra Stokholm and Manitta, Eleonora and Marques, Irene and Sørensen, Anja Elaine and Martino, David and Grunnet, Louise Groth and Kelstrup, Louise and Houshmand-Oeregaard, Azadeh and Clausen, Tine Dalsgaard and Mathiesen, Elisabeth Reinhardt and Olsen, Sjurdur Frodi and Saffery, Richard and Barrès, Romain and Damm, Peter and Vaag, Allan Arthur and Dalgaard, Louise Torp}},
issn = {{1868-7075}},
keywords = {{Adipose; Developmental programming; DNA methylation; Epigenetics; Gene expression; Gestational diabetes; Intrauterine hyperglycemia; Muscle; nc886; ncRNA; Type 1 diabetes; VTRNA2-1}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Clinical Epigenetics}},
title = {{Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy}},
url = {{http://dx.doi.org/10.1186/s13148-024-01673-3}},
doi = {{10.1186/s13148-024-01673-3}},
volume = {{16}},
year = {{2024}},
}