Appropriate glycemic management protects the germline but not the uterine environment in hyperglycemia.
Allan ZhaoHong JiangArturo Reyes PalomaresAlice LarssonWenteng HeJacob GrünlerXiaowei ZhengKenny Alexandra Rodriguez-WallbergSergiu-Bogdan CatrinaQiaolin DengPublished in: EMBO reports (2024)
Emerging evidence indicates that parental diseases can impact the health of subsequent generations through epigenetic inheritance. Recently, it was shown that maternal diabetes alters the metaphase II oocyte transcriptome, causing metabolic dysfunction in offspring. However, type 1 diabetes (T1D) mouse models frequently utilized in previous studies may be subject to several confounding factors due to severe hyperglycemia. This limits clinical translatability given improvements in glycemic control for T1D subjects. Here, we optimize a T1D mouse model to investigate the effects of appropriately managed maternal glycemic levels on oocytes and intrauterine development. We show that diabetic mice with appropriate glycemic control exhibit better long-term health, including maintenance of the oocyte transcriptome and chromatin accessibility. We further show that human oocytes undergoing in vitro maturation challenged with mildly increased levels of glucose, reflecting appropriate glycemic management, also retain their transcriptome. However, fetal growth and placental function are affected in mice despite appropriate glycemic control, suggesting the uterine environment rather than the germline as a pathological factor in developmental programming in appropriately managed diabetes.
Keyphrases
- glycemic control
- type diabetes
- mouse model
- blood glucose
- gene expression
- genome wide
- rna seq
- single cell
- healthcare
- public health
- dna methylation
- mental health
- weight loss
- insulin resistance
- dna repair
- endothelial cells
- birth weight
- dna damage
- cardiovascular disease
- high fat diet
- metabolic syndrome
- oxidative stress
- skeletal muscle
- health promotion
- induced pluripotent stem cells
- diabetic rats
- human health
- early onset
- transcription factor
- weight gain
- copy number
- physical activity
- drug induced