Type 1 diabetes affects zona pellucida and genome methylation in oocytes and granulosa cells

Mol Cell Endocrinol. 2020 Jan 15;500:110627. doi: 10.1016/j.mce.2019.110627. Epub 2019 Oct 19.


Diabetes affects oocyte nuclear and cytoplasmic quality. In this study, we generated a type 1 diabetes (T1D) mouse model by STZ injection to study the effects of T1D on zona pellucida and genomic DNA methylation of oocytes and granulosa cells. T1D mice showed fewer ovulated oocytes, reduced ovarian reserve, disrupted estrus cycle, and significantly ruptured zona pellucida in 2-cell in vivo embryos compared to controls. Notably, diabetic oocytes displayed thinner zona pellucida and treatment of oocytes with high concentration glucose reduced the zona pellucida thickness. Differential methylation genes in oocytes and granulosa cells were analyzed by methylation sequencing. These genes were significantly enriched in GO terms by GO analysis, and these GO terms were involved in multiple aspects of growth and development. Most notably, the abnormal methylation genes in oocytes may be related to oocyte zona pellucida changes in diabetic mice. These findings provide novel basic data for further understanding and elucidating dysgenesis and epigenetic changes in type 1 diabetes mellitus.

Keywords: DNA methylation; Diabetes; Oocyte; Zona pellucida.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • DNA Methylation*
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / metabolism
  • Epigenesis, Genetic
  • Estrous Cycle
  • Female
  • Gene Regulatory Networks
  • Granulosa Cells / chemistry*
  • Mice
  • Oocytes / chemistry*
  • Sequence Analysis, DNA
  • Streptozocin
  • Zona Pellucida / metabolism*


  • Streptozocin