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Type 2 diabetes impacts DNA methylation in human sperm
Lei Su1,2, Jonathan M Dreyfuss3, Rafael Ferraz Bannitz1
1Research Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Clinical Epigenetics
|March 20, 2025
Summary
Type 2 diabetes is linked to higher sperm DNA methylation in men, even with similar BMI. These epigenetic changes may impact offspring health, but further research is needed to determine reversibility with treatment.
Area of Science:
- Reproductive Biology
- Epigenetics
- Endocrinology
Background:
- Reproductive system disorders, including hypogonadism and reduced fertility, are under-recognized complications of diabetes.
- While mouse studies suggest hyperglycemia and obesity can alter sperm epigenetics, human data are limited.
- Type 2 diabetes (T2D) is associated with metabolic dysregulation impacting various bodily systems.
Purpose of the Study:
- To investigate the impact of type 2 diabetes and glycemic control on sperm quality and DNA methylation in humans.
- To compare sperm DNA methylation patterns between men with and without type 2 diabetes.
- To explore potential links between glycemic control (HbA1c) and differential DNA methylation in sperm.
Main Methods:
- Prospective cohort study involving 40 men (18 with T2D, 6 with prediabetes, 16 controls), all with BMI > 25 kg/m².
- Analysis of reproductive hormones, sperm concentration, and motility.
- Sperm DNA methylation profiling using MethylationEPIC BeadChip, with repeat sampling at 3 months in a subset of participants.
Main Results:
- Men with T2D exhibited higher follicle-stimulating hormone (FSH) but similar testosterone and sperm quality compared to controls.
- Sperm DNA methylation remained stable over 3 months in both diabetic and control groups.
- Differential methylation was observed at 655 CpG sites in men with T2D versus controls, with 96.5% showing increased methylation.
- Differentially methylated genes were associated with synaptic signaling, actin, cAMP, and G protein-coupled receptor pathways.
- 24% of differentially regulated probes overlapped with those linked to HbA1c.
Conclusions:
- Men with type 2 diabetes demonstrate elevated sperm DNA methylation levels compared to normoglycemic men with similar BMI.
- The clinical significance and potential reversibility of these epigenetic alterations with glucose-lowering treatments require further investigation.
- These findings highlight potential epigenetic contributions of T2D to reproductive health and offspring development.
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