In:
Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-2-14)
Abstract:
Growing evidence suggests that adverse intrauterine environments could affect the long-term health of offspring. Recent evidence indicates that gestational diabetes mellitus (GDM) is associated with neurocognitive changes in offspring. However, the mechanism remains unclear. Using a GDM mouse model, we collected hippocampi, the structure critical to cognitive processes, for electron microscopy, methylome and transcriptome analyses. Reduced representation bisulfite sequencing (RRBS) and RNA-seq in the GDM fetal hippocampi showed altered methylated modification and differentially expressed genes enriched in common pathways involved in neural synapse organization and signal transmission. We further collected fetal mice brains for metabolome analysis and found that in GDM fetal brains, the metabolites displayed significant changes, in addition to directly inducing cognitive dysfunction, some of which are important to methylation status such as betaine, fumaric acid, L-methionine, succinic acid, 5-methyltetrahydrofolic acid, and S-adenosylmethionine (SAM). These results suggest that GDM affects metabolites in fetal mice brains and further affects hippocampal DNA methylation and gene regulation involved in cognition, which is a potential mechanism for the adverse neurocognitive effects of GDM in offspring.
Type of Medium:
Online Resource
ISSN:
2296-634X
DOI:
10.3389/fcell.2022.748862
DOI:
10.3389/fcell.2022.748862.s001
DOI:
10.3389/fcell.2022.748862.s002
DOI:
10.3389/fcell.2022.748862.s003
DOI:
10.3389/fcell.2022.748862.s004
DOI:
10.3389/fcell.2022.748862.s005
DOI:
10.3389/fcell.2022.748862.s006
DOI:
10.3389/fcell.2022.748862.s007
DOI:
10.3389/fcell.2022.748862.s008
DOI:
10.3389/fcell.2022.748862.s009
DOI:
10.3389/fcell.2022.748862.s010
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2737824-X
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